Superior Survival after Autologous vs. Allogeneic Hematopoietic Stem Cell Transplantation (HCT) for Diffuse Large B-Cell Lymphoma (DLBCL) Not Explained by Differences in Chemosensitivity.

Blood ◽  
2006 ◽  
Vol 108 (11) ◽  
pp. 3021-3021
Author(s):  
Brandon Hayes-Lattin ◽  
Jeanette Carreras ◽  
Mei-Jie Zhang ◽  
Koen van Besien ◽  
Julie M. Vose ◽  
...  
Keyword(s):  
B Cell Lymphoma ◽  
Older Age ◽  
Disease Stage ◽  
Hematopoietic Stem ◽  
Post Transplant ◽  
Significant Difference ◽  
Risk Of Progression ◽  
The Difference ◽  
Induction Failure ◽  
Autologous Hct

Abstract No randomized trials have compared autologous HCT (autoHCT) to allogeneic HCT (alloHCT) for DLBCL. We analyzed the outcomes of 916 patients (pts) (837 autoHCT and 79 alloHCT) ages 18–60yrs after a first autoHCT or HLA-identical sibling alloHCT for DLBCL between 1995 and 2003 reported to the CIBMTR. Pts receiving T-cell depleted allografts or reduced-intensity conditioning were excluded. There were significant baseline differences between the groups in disease stage, B symptoms, extranodal disease and marrow involvement. AlloHCT pts were significantly more likely to have >3 chemo regimens prior to HCT (53 vs 40%), and resistant induction failure or relapse (39 vs 16%). At 1yr, treatment-related mortality (TRM) was higher after alloHCT (41%, 95% CI, 30–52%) than after autoHCT (11%, 95% CI, 9–14%, p<0.001), but risks of relapse/progression were similar (30%, 95% CI, 21–41%) and (33%, 95% CI, 29–36%, p=0.69), respectively. Cumulative incidence of outcomes and univariate probabilities of progression free (PFS) and overall survival (OS) at 5 yrs are summarized in table 1. In multivariate analysis, allo and autoHCT had differential early and late effects on outcomes. In the first 12 mo after transplant, alloHCT was associated with higher TRM (RR 4.76, 95% CI, 3.14–7.22, p<0.001), treatment failure (RR 2.08, 95% CI, 1.56–2.77, p<0.001) and mortality (RR 2.78, 95% CI, 2.06–3.77, p<0.001) but similar risk of progression (RR 1.14, 95% CI, 0.75–1.74, p=0.54) compared to autoHCT. Among pts surviving 12 mo post-transplant, no significant difference was observed between autoHCT and alloHCT for TRM, progression, PFS, or OS. Covariates that increased the risks of TRM and OS were older age (51–60 years), KPS <90%, chemoresistance at transplant, and earlier transplant yr (before 2001 vs later). Older age and chemoresistance were also associated with progression and lower PFS. There were no significant interactions between graft type and other prognostic variables; in particular, relative risk of outcomes with allo vs autoHCT were similar for patients with chemosensitive and chemoresistant disease. In summary, myeloablative alloHCT increased risks of early TRM and mortaliy without an effect on progression (compared to autoHCT). Transplant type did not affect outcomes after 12 months post-transplant. AutoHCT was associated with superior survival (fig 1), and the difference was not explained by differences in chemosensitivity at the time of transplant. AutoHCT AlloHCT Outcomes (95%CI) (95%CI) AGVHD @ day 100 N/A 42 (31–53) CGVHD @ 5yrs N/A 27 (18–38) TRM @ 5yrs 18 (15–20) 45 (34–57) Relapse/progression @ 5yrs 39 (36–43) 33 (23–44) PFS @ 5yrs 43 (40–46) 26 (18–37) OS @ 5yrs 49 (46–53) 27 (18–27) Figure 1 Figure 1.

Factors Affecting the Development of Atrial Fibrillation and Atrial Flutter (AF) Following Autologous Hematopoietic Stem Cell Transplantation (auto-HSCT).

Blood ◽  
2005 ◽  
Vol 106 (11) ◽  
pp. 1754-1754
Author(s):  
Mary Lee H. Villanueva ◽  
Fausto R. Loberiza ◽  
James O. Armitage ◽  
Robert G. Bociek ◽  
Apar Kishor Ganti ◽  
...  
Keyword(s):  
Serum Creatinine ◽  
Multivariate Model ◽  
Disease Stage ◽  
Hematopoietic Stem ◽  
Post Transplant ◽  
Factors Associated ◽  
Mediastinal Irradiation ◽  
Number Of Patients ◽  
Significant Difference ◽  
History Of

Abstract Background: The use of auto-HSCT has expanded to include older patients. Age is a risk factor for the development of AF in the general population. As more elderly patients undergo auto-HSCT, the risk of developing AF post-transplant may also increase. The development of AF may increase morbidity, may prolong hospitalization, and may increase the cost of hospitalization. However, few data exist evaluating the factors that contribute to the development of AF following auto-HSCT. At our institution, we have observed a large number of patients with this complication. Therefore, we performed a retrospective case-control study to determine the incidence of AF following auto-HSCT and to determine risk factors associated with the development of AF. Patients and Methods: We performed a chart review on all patients at our institution who received an auto-HSCT from November 1999 to May 2004. Cases were identified by reviewing EKGs performed post-transplant. Controls consisted of patients with similar age, year of transplant, and underlying hematologic malignancy. The following variables were examined for their association with AF: age, sex, diagnosis, disease stage at transplant, conditioning regimen, year of transplant, previous medical history including cardiac history, pre-transplant cardiology work-up, and electrolyte abnormalities immediately following auto-HSCT. Patients who developed AF were compared to controls. Multivariate logistic regression was done to evaluate the factors associated with the development of AF. Results: During the study period, 44 patients developed AF at a median of four days (range days 1–9) following auto-HSCT; incidence of 8.5%. We identified 516 patients who did not develop AF who had auto-HSCT in the same time period. Of these, 179 patients with similar characteristics were used as controls. The following variables were associated with developing AF in the multivariate model: age at transplant; median age 63 yrs (50–72) for cases vs 57 (49–72) for controls (p&lt;0.001), abnormal renal function as determined by serum creatinine (p=0.008), history of previous arrhythmia (p&lt;0.001), and a history of mediastinal irradiation (p=0.003). Although not significant in the multivariate model, we observed that 45% of the patients who developed AF had increased left atrial size on a pre-transplant echocardiogram as opposed to none in the controls (p&lt;0.001). There was no difference in the length of hospital stay between the cases and controls (p=0.13). We did not detect a significant difference in the 100d survival between those who did and did not develop AF (90% vs 96%, p=0.25). However, patients who did not develop AF had a better overall survival (Log-rank p=0.04). Conclusions: Patients with older age, elevated serum creatinine level, history of previous arrhythmia, or history of previous mediastinal irradiation are more likely to develop AF following an auto-HSCT. Future studies should investigate whether interventions such as prophylactic beta-blockers can decrease the incidence of AF following auto-HSCT.

scholarly journals Does Addition of Rituximab (R) to BEAM Conditioning Improve Outcomes of Patients with Diffuse Large B-Cell Lymphoma (DLBCL) Undergoing Autologous Hematopoietic Cell Transplantation (auto-HCT)?

Blood ◽  
2019 ◽  
Vol 134 (Supplement_1) ◽  
pp. 785-785
Author(s):  
Deepa Jagadeesh ◽  
Navneet S. Majhail ◽  
He Yizeng ◽  
Kwang Woo Ahn ◽  
Carlos Litovich ◽  
...  
Keyword(s):  
Board Of Directors ◽  
Cumulative Incidence ◽  
Research Funding ◽  
B Cell Lymphoma ◽  
Older Age ◽  
Disease Stage ◽  
Karnofsky Performance Score ◽  
Advisory Committees ◽  
Significant Difference ◽  
The Impact

Introduction: Rituximab-based high-dose therapy (HDT) is frequently prescribed to DLBCL patients (pts) undergoing auto-HCT. However data supporting the benefit of adding R to auto-HCT conditioning are not available. Herein, we report the impact of R-based conditioning on auto-HCT outcomes of DLBCL pts. Methods: Using the Center for International Blood and Marrow Transplant Research registry, 862 adult (≥18 years) DLBCL pts undergoing auto-HCT, between 2003-2017 were included. Analysis was limited to pts receiving BEAM (BCNU, etoposide, cytarabine, melphalan)-based HDT, as R was infrequently used with non-BEAM conditioning regimens. All pts received R-containing chemoimmunotherapy in the frontline setting and had chemosensitive disease prior to HCT. Early chemoimmunotherapy failure (ECitF) was defined as not achieving a complete remission (CR) after frontline chemoimmunotherapy or relapsing within 1 year of initial diagnosis. Primary outcome was overall survival (OS). Secondary outcomes included non-relapse mortality (NRM), relapse, progression-free survival (PFS) and infectious complications within 100 days post-HCT. Results: The study cohort was divided into 2 groups; BEAM (n=667) and R-BEAM (n=195). The baseline characteristics of the 2 cohorts were comparable including age at auto-HCT, disease stage, Karnofsky performance score, extranodal involvement, time from diagnosis to auto-HCT, number of prior therapies, remission status, and ECitF. However, significantly more R-BEAM cohort patients received R as part of last therapy line before auto-HCT (75% vs. 86%; P=0.001). Median follow-up of survivors was 48 (range 1-171) and 64 (range 3-142) months in the BEAM and R-BEAM cohorts, respectively. On univariate analysis, the 4 year cumulative incidence of relapse (41% vs 44%), NRM (11% vs 9%), PFS (48% vs 47%; Figure 1) and OS (58% vs 61%; Figure 2) were similar in the R-BEAM and BEAM groups, respectively (Table 1). On multivariate analysis, no significant difference was seen in OS (HR 0.81; 95% CI 0.81-1.31; P=0.83) or PFS (HR 0.94; 95% CI 0.76-1.18; P=0.61) (Table 1) between the two cohorts. Addition of R had no impact on risk of relapse (HR 0.83; 95% CI 0.65-1.07; P=0.15) or NRM (HR 1.43; 95% CI 0.909-2.26; P=0.12). Variables independently associated with lower OS included older age (HR 3.05; 95% CI 1.81-5.13; P&lt;0.001), not being in CR at auto-HCT (HR 1.67, 95% CI 1.39-2.07; P&lt;0.001) and presence of ECitF (HR 1.52, 95% CI 0.54-3.26; P&lt;0.001). Older age (HR 2.26, 95% CI 1.48-3.45; P&lt;0.0002) and not being in CR at auto-HCT (HR 1.78, CI 1.47-2.14; P&lt;0.0001) were also associated with inferior PFS. There was no significant difference in the 100-day cumulative incidence of bacterial, viral or fungal infections between the two cohorts. Disease relapse was the main cause of death in both BEAM and R-BEAM cohorts (66% vs 55%). Conclusion: In this large registry analysis of DLBCL pts undergoing auto-HCT, adding R to BEAM conditioning had no impact on transplantation outcomes. Older age, absence of CR and ECitF were associated with inferior survival. Disclosures Majhail: Mallinckrodt: Honoraria; Incyte: Consultancy; Nkarta: Consultancy; Anthem, Inc.: Consultancy; Atara Bio: Consultancy. Sureda:Janssen: Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: Travel Support; Gilead: Honoraria; Amgen: Membership on an entity's Board of Directors or advisory committees; Takeda: Consultancy, Honoraria, Speakers Bureau; Novartis: Honoraria; BMS: Honoraria; Roche: Honoraria; Sanofi: Honoraria; Celgene: Honoraria, Membership on an entity's Board of Directors or advisory committees. Kharfan-Dabaja:Daiichi Sankyo: Consultancy; Pharmacyclics: Consultancy. Hamadani:ADC Therapeutics: Consultancy, Research Funding; Merck: Research Funding; Takeda: Research Funding; Pharmacyclics: Consultancy; Celgene: Consultancy; Medimmune: Consultancy, Research Funding; Janssen: Consultancy; Otsuka: Research Funding; Sanofi Genzyme: Research Funding, Speakers Bureau.

The Impact of Molecular Lesions in Post-Transplant Acute Myeloid Leukemia (AML) in Correlation with Cytogenetic Abnormalities,

Blood ◽  
2011 ◽  
Vol 118 (21) ◽  
pp. 4137-4137
Author(s):  
Nelli Bejanyan ◽  
Brian J. Bolwell ◽  
Edward A. Copelan ◽  
Lisa Rybicki ◽  
Hideki Makishima ◽  
...  
Keyword(s):  
Clinical Outcomes ◽  
Older Age ◽  
Prognostic Impact ◽  
Intermediate Risk ◽  
Hematopoietic Stem ◽  
Npm1 Mutation ◽  
Secondary Aml ◽  
Post Transplant ◽  
Significant Difference ◽  
The Impact

Abstract Abstract 4137 Relapse remains the most common cause of treatment failure in allogeneic hematopoietic stem cell transplantation (AlloHCT) for AML. Several risk factors (i.e. older age, persistent disease at transplant, adverse cytogenetics, secondary AML, non-myeloablative conditioning regimen) have been identified as predictors for post-transplant AML recurrence. In addition, the adverse prognostic influence of specific mutations (DNMT3, ASXL1, IDH1/2, RUNX1, TET2, TP53 etc.) has been identified in both de novo and secondary AML treated with standard chemotherapy regimens. The impact of these mutations on clinical outcomes following AlloSCT, however, remains largely unexplored. Consequently, we conducted this study to investigate the prognostic role of molecular lesions including metaphase (MC) and SNP array (SNP-A) cytogenetic defects and somatic mutations in patients undergoing AlloHCT. A total of 186 patients were identified who received myeloablative AlloHCT for AML (2000–2010) and had pre-transplant diagnostic leukemic sample available for testing. We performed SNP-A karyotyping and sequencing for RUNX1, DNMT3, TP53, ASXL1, CBL, IDH1/2, NPM1, FLT3ITD and TET2 gene mutations and correlated the results with clinical outcomes following AlloHCT. SNP-A based karyotyping helped to upstage the cytogenetics by inclusion of previously undetected cryptic abnormalities.Cox proportional hazards analysis was used to identify prognostic factors for relapse, relapse free (RFS) and overall survival (OS). Analysis was based on 103 patients (55%) who had data on cytogenetics. Of these 103 patients, 42 (41%) had disease relapse following transplantation and 58 (56%) died within the median follow up of 39 months (range, 8–133) following their myeloablative AlloSCT. The frequencies of mutations were estimated; for example, FLT3, NPM1, DNMT3, ASXL1, IDH1/2, CBL, RUNX1 and TP53 were detected in 18%, 13%, 14%, 9%, 9%, 4%, 2% and 2% of the cases, respectively. Overall, mutations were present in 35% of AML cases, and were exclusive to those with intermediate or favorable risk cytogenetics. Various combinations were encountered, however in those with 2 concomitant mutations, NPM1 was present in all cases. In patients with intermediate risk cytogenetics (n=83) and those with mutational abnormalities the leukemia relapse rate was 40% and 38%, respectively. In particular, among patients harboring NPM1 mutation relapses occurred in those who were positive for either DNMT3 or FLT3ITD. Lower rate of relapse (25%) was observed in patients with ASLX1 and IDH1/2 mutations. In one case of aggressiveTP53 mutation the patient was alive and leukemia free 3 years after her AlloHCT. In multivariable analysis, complex cytogenetics was an independent predictor for inferior RFS (HR=1.97, 95% CI, 1.04–3.7) and OS (HR=1.96, 95% CI, 1.04–3.7).Older age at transplant (per 10 yr increase, HR=1.24, 95% CI, 1.01–1.5) was associated with poorer OS, whereas higher comorbidity score (HR=1.86, 95% CI, 1.04–3.3) was associated with poorer RFS. There was no significant difference in post-transplant outcomes between patients in intermediate risk cytogenetics with detected genetic mutations (excluding isolated NPM1) and those with no detectable mutations. Our preliminary results suggest that myeloablative AlloHCT could minimize the prognostic impact of adverse molecular markers in AML. These mutations potentially serve as important biomarkers in determining the management of AML. Further studies designed to determine their precise role are planned. Disclosures: No relevant conflicts of interest to declare.

Pre-Transplant Rituximab Therapy Is Associated with Improved Progression-Free and Overall Survival in Patients Undergoing Autologous Hematopoietic Stem Cell Transplantation for Diffuse Large B-Cell Lymphoma (DLBCL).

Blood ◽  
2007 ◽  
Vol 110 (11) ◽  
pp. 19-19 ◽  
Author(s):  
Timothy S. Fenske ◽  
Parameswaran Hari ◽  
Jeanette Carreras ◽  
Mei-Jie Zhang ◽  
Rammurti Kamble ◽  
...  
Keyword(s):  
Overall Survival ◽  
Stem Cell ◽  
Hematopoietic Stem Cell Transplantation ◽  
Stem Cell Transplantation ◽  
Cell Transplantation ◽  
Hematopoietic Stem Cell ◽  
B Cell Lymphoma ◽  
Hematopoietic Stem ◽  
Post Transplant ◽  
Conditioning Therapy

Abstract Outcomes following first-line therapy for patients (pts) with DLBCL have improved significantly with the availability of the chimeric anti-CD20 monoclonal antibody rituximab (R). Despite this progress, many pts develop refractory or recurrent DLBCL and are considered candidates for autologous hematopoietic stem cell transplantation (AuHCT). For such pts, it is possible that R given pre-transplant and/or during conditioning therapy affects the natural history of DLBCL, such that traditional methods of risk assessment and patient selection for AuHCT may need revision. We therefore studied the outcomes of 1,006 pts who underwent peripheral blood AuHCT for DLBCL between 1996 and 2003 reported to the CIBMTR, analyzed according to whether R was (n=188, “+R” group) or was not (n=818, “-R” group) administered prior to AuHCT. Using the chi-square statistic for categorical and the Kruskal-Wallis for continuous variables, there were no significant differences between the +R and -R groups with regard to gender, pre-transplant performance status, disease status at transplant, pre-transplant chemosensitivity, second-line aa-IPI score distribution, Ann Arbor stage at transplant, interval from diagnosis to transplant, bulky disease, bone marrow involvement, post-transplant radiation therapy, or post-transplant myeloid growth factor therapy. The +R group had a higher proportion of pts age 61 or older (40% vs. 23%, p&lt;0.001). AuHCT occurred between 1999–2003 in 96% of pts in the +R group, and between 1996–2001 in 93% of the -R pts (p&lt;0.001). For the +R pts, 94% received R only with pretransplant chemotherapy, 3% only with conditioning therapy, and 3% with both pretransplant chemotherapy and conditioning therapy. Conditioning regimens were similar in the +R and -R groups, with the majority receiving the BEAM regimen. In univariate analysis, platelet and neutrophil engraftment were not affected by use of R. Treatment-related mortality (TRM) at 1, 3, or 5 years did not differ significantly between the +R and -R groups. Progression-free survival (PFS) at 1 and 3 years was superior in the +R group (62% vs. 49% at 1 year, p=0.002; 49% vs. 38% at 3 years, p=0.010). Overall survival (OS) was superior in the +R group (68% vs. 60% at 1 year, p=0.032; 57% vs. 45% at 3 years, p=0.003). In multivariate analysis, later year of transplant (2000–2003) and age &lt;55 were associated with lower TRM, but pre-transplant R was not. Conversely, pre-transplant R, age &lt;55, and fewer than 3 lines of chemotherapy were associated with improved PFS, while year of transplant was not. Finally, pre-transplant R, age &lt;55, fewer than 3 lines of chemotherapy, and year of transplant 2000–2003, were all associated with improved OS. We conclude that pre-transplant rituximab is associated with improved PFS and OS following AuHCT for DLBCL, with no evidence of impaired engraftment or increased TRM.

Disease Characteristics and Patterns of Care In Elderly Patients (80+ years) with Follicular Lymphoma (FL) In the United States (US); Are Older Patients Treated Differently? Report From the National LymphoCare Study (NLCS)

Blood ◽  
2010 ◽  
Vol 116 (21) ◽  
pp. 4152-4152
Author(s):  
Chadi Nabhan ◽  
Michelle Byrtek ◽  
Michael Taylor ◽  
Jill Tydell ◽  
Jamie H. Hirata ◽  
...  
Keyword(s):  
Older Patients ◽  
Research Funding ◽  
Age Groups ◽  
Treatment Patterns ◽  
Disease Stage ◽  
Younger Patients ◽  
Disease Characteristics ◽  
Significant Difference ◽  
The Difference ◽  
Grade 3

Abstract Abstract 4152 Background: While FL is the most common low-grade lymphoma in the US, median age was less than 60 in patients enrolled on pivotal studies that led to our understanding of disease biology and optimal therapy. It remains unclear whether similar disease characteristics, presentation, prognostic factors, treatment patterns, and outcomes pertain to older patients with FL. No clear guidelines exist on how older patients should be treated and data is lacking as to whether current practice patterns affect their survival and progression. Previous reports on FL in the elderly have been retrospective and single center-based. Methods: The NLCS is a prospective, longitudinal multicenter, observational study that enrolled consecutive newly diagnosed FL patients from 3/2004 through 3/2007 collecting data on disease and patients' characteristics, treatment patterns, and outcome. Using the NLCS data we analyzed information on disease stage, grade, FL International Prognostic Index (FLIPI), B symptoms, and treatment choice for patients <60 years, 60–69 years, 70–79 years, and 80+ years. Either Chi-square or Fisher's exact comparison was used to assess the correlations depending on the sample size of the test. Results: A total of 2,736 pts were enrolled, of which 1,215 (44%) were < 60, 708 (25%) were between 60–69, 549 (20%) were between 70–79, and 264 (9%) were >80. There was a significant difference in grade distribution across the different age groups (p < 0.0001), with 22% of pts 80+ having grade 3 FL vs 17% pts <60. No significant differences across age groups in B symptoms, extra nodal sites, or LDH values were observed. A significant difference in FLIPI score was seen across the age groups (p < 0.0001) where high-score FLIPI was present in 48% of pts 80+ as opposed to 16% of pts <60, although calculating FLIPI might be confounded by the fact that older patients were more likely to not have received a bone marrow (BM) exam with 66% of pts 80+ not having BM exam vs. only 40% of those <60 (p < 0.0001). The difference in FLIPI was mainly due to lower Hgb values as older patients were more likely to have had Hgb < 12 g/dL than younger patients (31% of pts 80+ vs. 15% of pts <60) and to age being a component of the FLIPI index. The difference in FLIPI score across age groups was also observed in patients with grade 3 FL where 53% of pts 80+ had poor FLIPI vs. 15% of pts <60 (p < 0.0001). A statistically significant difference in treatment patterns was found across age groups (p <0.0001). When treatment was implemented, older patients were more likely to have received rituximab (R) monotherapy (37% of 80+ vs. 12% of <60) and less likely to have received R+Chemotherapy (40% of pts 80+ vs. 64% of pts<60). In addition, more pts 80+ were observed compared to those <60 (23% vs. 16%). These differences persisted even in those with advanced stage (III/IV), grade 3 disease, region of diagnosis, and in poor-risk FLIPI. When chemotherapy was used, older patients were less likely than younger patients to receive anthracyclines (p < 0.0001) (31% of pts 80+ vs. 69% of pts<60). Anthracycline use remained significantly different regardless of disease stage, grade, or FLIPI score. Conclusions: To our knowledge, this is the largest prospective data collection available for FL pts 80+ years of age. We demonstrate that these pts have higher FLIPI score and grade 3 disease. When treatment is initiated, these patients receive R monotherapy more often than their younger counterpart. Anthracycline use in this population is also less common regardless of disease stage, grade, or risk profile. Whether these baseline differences translate into different outcomes remains to be seen. Disclosures: Nabhan: genentech: Research Funding, Speakers Bureau. Byrtek:Genentech: Employment. Taylor:Genentech: Employment. Hirata:Genentech: Employment. Flowers:Genentech/Biogen-Idec (unpaid): Consultancy; Celgene, Intellikine: Consultancy; Millennium: Research Funding.

Superior Outcome Using Cyclosporin A Alone Versus Cyclosporin A Plus Methotrexate for Post-Transplant Immunosuppression In Children with Acute Leukemia Undergoing Hematopoietic Stem Cell Transplantation.

Blood ◽  
2010 ◽  
Vol 116 (21) ◽  
pp. 4502-4502
Author(s):  
Bernd Gruhn ◽  
Melissa Weiß ◽  
Ilona Wolff ◽  
Felix Zintl ◽  
James F. Beck
Keyword(s):  
Stem Cell ◽  
Hematopoietic Stem Cell Transplantation ◽  
Cyclosporin A ◽  
Cumulative Incidence ◽  
Chronic Gvhd ◽  
Hematopoietic Stem ◽  
Post Transplant ◽  
Graft Versus Leukemia ◽  
Significant Difference ◽  
Graft Versus Leukemia Effect

Abstract Abstract 4502 Graft-versus-host disease (GVHD) is a major complication and one of the main causes of death after hematopoietic stem cell transplantation (HSCT). The GVHD prophylaxis influences the incidence of GVHD, relapse rate, and patient's survival. GVHD is associated with graft-versus-leukemia effect, which is mediated by donor T lymphocytes and decreases the risk of relapse. Therefore, a reduced post-transplant immunosuppression might have a positive impact on patient's survival. The outcome of different immunosuppressive prophylaxis regimen for adult patients has been studied extensively, whereas the effect on children has yet to be determined. Therefore, we performed a retrospective study analyzing 62 children (median age, 11 years) with acute lymphoblastic leukemia (n=35) or acute myeloid leukemia (n=27) who underwent bone marrow (n=56), peripheral blood stem cell (n=4), or umbilical cord blood (n=2) transplantation in a single center between November 1984 and July 2008. All respective donors were HLA-identical siblings. The patients received an immunosuppressive prophylaxis consisting of cyclosporin A (CSA) plus methotrexate (MTX) (n=43) or cyclosporin A alone (n=19). Patients in the CSA+MTX arm received CSA at a total dose of 10 mg/kg/day on day -1, 5mg/kg/day on days 0 to 4, and 3 mg/kg/day starting on day 5, and in addition MTX at a dosage of 10 mg/m2 on days 1, 3, 6, and 11. The 19 patients in the CSA arm received CSA at a total dose of 3 mg/kg/day starting on day -1. Concerning the patient's gender, age, diagnosis, and state of remission prior to transplantation, the two groups did not differ significantly. Patients who received CSA alone as post-transplant immunosuppression had a significantly reduced cumulative incidence of relapse (5% versus 40%; p=0,002), a significantly increased 5-year event-free survival (84% versus 35%; p=0.001), and a significantly increased 5-year overall survival (84% versus 42%; p=0.004). Interestingly, the incidence of acute GVHD grade II-IV in patients in the CSA arm was equivalent to the CSA+MTX arm (26% versus 19%; p=0.440). In addition, we did not observe a significant difference in the cumulative incidence of chronic GVHD (32% in the CSA arm versus 23% in the CSA+MTX arm; p=0.428). There was also no significant difference in the cumulative incidence of treatment related mortality after 1 year (10% in the CSA arm versus 23% in the CSA+MTX arm; p=0.165). In conclusion, CSA alone for post-transplant immunosuppression allows a stronger graft-versus-leukemia effect and thereby reduces the relapse rate and the number of patients dying of leukemia effectively without increase of acute and chronic GVHD. Post-transplant immunosuppression consisting of CSA alone leads to a superior outcome and should be preferred in children with a HLA-identical sibling as donor. Disclosures: No relevant conflicts of interest to declare.

Prognostic Impact of Physiological B-Cell Precursors (hematogones) in the Bone Marrow As Determined by Immunophenotyping in the Post-Transplant Period in Patients with AML

Blood ◽  
2012 ◽  
Vol 120 (21) ◽  
pp. 1406-1406
Author(s):  
Ulrike Bacher ◽  
Maximilian Christopeit ◽  
Anneke Heiland ◽  
Mascha Binder ◽  
Tatjana Zabelina ◽  
...  
Keyword(s):  
Bone Marrow ◽  
B Cell ◽  
Risk Group ◽  
Disease Stage ◽  
Prognostic Impact ◽  
Myeloid Malignancies ◽  
Post Transplant ◽  
Significant Difference ◽  
The Mean ◽  
B Cell Precursors

Abstract Abstract 1406 Aiming to improve post-transplant monitoring strategies for patients with acute myeloid leukemia (AML) or myelodysplastic syndromes (MDS), approaches to monitor the minimal residual disease load are at present limited to distinct genetic subgroups, e.g. NPM1mut AML. In the conservative treatment setting, increased levels of physiologic B-cell precursors (>0.01% CD10+/CD19+ cells; “hematogones”) as determined by multiparameter flow cytometry (MFC) in the bone marrow (BM) were suggested to be favorable in AML pts (Chantepie et al., Blood, 2011). We investigated whether the prognostic impact of physiologic B-cell precursors can be confirmed in pts with myeloid malignancies in the transplant context. We quantified CD10+/CD19+ B-cell precursors by MFC in the post-transplant period in 76 pts with AML/MDS who received allogeneic hematopoietic stem cell transplantation (HSCT) at Hamburg University, and performed correlation with survival (41 m/35 f; 18–71 yrs; de novo AML: n=51; s-/t-AML: n=11; MDS: n=13). The majority (n=84, 73%) received reduced intensity conditioning (RIC), mainly based on the FLAMSA regimen. Hematogones were evaluated by MFC on days +30 (d30) and +100 (d100) post-HSCT including the following antibody panel: CD19+, CD10+, CD34+, TdT+. Median levels of CD10+/CD19+ cells were 0,06% on day 30 (mean, 0.25%; range, 0–2.4%) and 1.55% on day 100 (mean, 2.13%; range, 0–12.4%). OS from HSCT did not differ on the basis of the CD10+/CD19+ cells measured on d30 (mean±SD=61±6 weeks, for CD10+/CD19+ cells below the mean of 0.25% vs 74±13 weeks for CD10+/CD19+ cells above the mean, RR=0.73, p=0.685). Estimated 1-year-OS±SE was 63±10% for CD10+/CD19+ cells below the mean of 0.25% versus 71±17% for CD10+/CD19+ cells above the mean, respectively. EFS did not show a significant difference, either. Mean CD10+/CD19+ cells on day 100 associated positively with 1-year-OS. In the group below the mean CD10+/CD19+ cells of 2.13%, 1-year-OS±SE was estimated to be 69±9% (median±SEM=89±10 weeks) which was worse when compared to the group above the mean with a 1-year-OS±SE of 83±15% (median±SEM=96±8 weeks; RR=0.124, p=0.046). The effect of low versus high CD10+/CD19+ cells measured at day 100 on EFS was even more pronounced. 1-year-EFS was significantly worse with 60±10% in the group with lower CD10+CD19+ counts on day 100 versus 95±4% in the group with higher counts (RR=0.095, 95%CI=0.012–0.728, p=0.024). In univariate analysis, disease stage, remission status pre-HSCT, cytogenetic risk group and cGVHD had significant influence on OS and/or EFS. By multivariate analysis, CD10+/CD19+ cells on day 100 remained significantly associated with improved EFS (RR=0.998, p=0.001) but significance of the association with OS was lost (RR=0.145, p=0.07). Other factors significantly associated with superior OS and EFS were occurrence of cGVHD (OS: RR=0.997, p=0.049, EFS: RR=0.996, p=0.001), and low/intermediate cytogenetic risk group (OS: RR=0.995, p=0.005, EFS: RR=0.997, p=0.03). To the best of our knowledge, an association of CD10+/CD19+ cells measured by MFC with survival has not been performed after HSCT in pts with AML and MDS. Our study is the first one showing a favorable prognostic impact of increased CD10+/CD19+ cells 100 days after HSCT. It seems that the level of physiological precursors contributes to the prognostic parameters in patients with myeloid malignancies undergoing HSCT. In more detail, a proportion of more than 2.13% of hematogones at day 100 was associated with improved OS and EFS. The association remained positive in multivariate Cox regression analysis, when other parameters such as pre-transplant permission status, disease stage and cGvHD were included. In conclusion, the hematogones level at day 100 seems to be an independent prognostic parameter which should be further evaluated in pts with myeloid malignancies undergoing HSCT. Considering the experience needed for the determination of leukemia associated immunophenotypes by MFC, or the lack of molecular markers suitable for MRD monitoring in many AML and MDS patients, the introduction of hematogones measurement at defined time points may contribute to the identification of high-risk patients in the transplant context. Disclosures: Bacher: MLL Munich Leukemia Laboratory: Employment. Haferlach:MLL Munich Leukemia Laboratory: Equity Ownership.

Alkylator-Based Conditioning for Allogeneic Hematopoietic Stem Cell Transplantation (alloHSCT) in Lymphoma: A Registry Study Comparing Thiotepa-, Busulfan-, Melphalan- and Treosulfan-Containing Regimens On Behalf of the EBMT Lymphoma Working Party

Blood ◽  
2012 ◽  
Vol 120 (21) ◽  
pp. 2033-2033
Author(s):  
Peter Dreger ◽  
Herve Finel ◽  
Renato Fanin ◽  
Paolo Corradini ◽  
Michele Falda ◽  
...  
Keyword(s):  
Cell Lymphoma ◽  
Performance Status ◽  
Conditioning Regimen ◽  
Working Party ◽  
B Cell Lymphoma ◽  
Poor Performance Status ◽  
Unrelated Donor ◽  
Hematopoietic Stem ◽  
Remission Status ◽  
Significant Difference

Abstract Abstract 2033 Background: Thiotepa (TT) is an alkylating agent approved for conditioning for alloHSCT. TT-based alloHSCT has been pioneered in a variety of lymphoma subtypes with promising results, but the available information about the value of thiotepa in this indication compared to other alkylator-based regimens is still limited. Primary objective was to compare the outcome of TT-based alloHSCT with that of alloHSCT conditioned with other alkylator regimens (non-TT) separately for diffuse large B-cell lymphoma (DLBCL), follicular lymphoma (FL), and peripheral T Cell lymphoma (PTCL). Primary endpoint was event-free survival (EFS); secondary endpoints were overall survival, non-relapse mortality (NRM), and relapse incidence. Eligible were patients >18 years who had received TT-, busulfan (BU)-, melphalan- (MEL), or treosulfan- (TREO) based conditioning for T-replete alloHSCT between 2003–2010 for FL, DLBCL, or PTCL. Statistical analysis was based on multivariable comparisons using stratified Cox and Fine & Gray regression models. Results: 201 patients with TT fulfilled the inclusion criteria and were compared with 578 non-TT patients (BU 55%, MEL 35%, TREO 10%). The most frequently used specific regimens were TT-cyclophosphamide combinations (75%) in the TT group and BU-fludarabine combinations (52%) in the non-TT group. Of the total 779 patients, 43%% had FL, 39% DLBCL, and 18% PTCL. TT and non-TT patients were comparable for age, sex, time from diagnosis, remission status at HSCT, and proportion of unrelated donor transplants. However, the TT group contained significantly more patients with PTCL (24% vs 15%), with poor performance status (PS; 12.5% vs 3%), and with BM as HSCT source (14% vs 9%). By multivariate comparisons considering conditioning, age, sex, remission status, PS, and time from diagnosis, EFS was significantly affected by active disease at HSCT and poor PS in all three lymphoma subtypes. In contrast, conditioning with TT had no significant impact (Hazard ratio (HR) 1.06 (0.67–1.67) for FL; 1.01 (0.67–1.51) for DLBCL; 1.33 (0.75–2.36 for PTCL) on EFS or any other endpoint. Similar results were seen when the analysis was broken down to specific conditioning regimens (TT-CY vs BU-based). MEL- and TREO-based regimens did not show a significant difference compared to BU for any endpoint. Conclusions: This study failed to identify significant outcome differences between the four conditioning regimen types tested. However, the limitations inherent to registry analyses have to be considered. In particular, conclusions on differential regimen toxicity apart from NRM will require additional, ideally prospective studies. Disclosures: Dreger: Riemser G, Greifswald, Germany: Consultancy, Honoraria, Research Funding. Off Label Use: Treosulfan for conditioning for allogeneic HSCT. Schmitz:Riemser AG, Greifswald, Germany: Honoraria.

Pre-/Post-HSCT Imatinib Improves Survival of Childhood with BCR/ABL+ Acute and Chronic Leukemia

Blood ◽  
2014 ◽  
Vol 124 (21) ◽  
pp. 5248-5248
Author(s):  
Fuyu Pei ◽  
Qi Li ◽  
Wenfeng Xu ◽  
Zhiyong Peng ◽  
Xuedong Wu ◽  
...  
Keyword(s):  
Stem Cells ◽  
Stem Cell ◽  
Myeloid Leukemia ◽  
Myelogenous Leukemia ◽  
Hematopoietic Stem ◽  
Post Transplant ◽  
Stem Cell Source ◽  
Significant Difference ◽  
Cell Source

Abstract Objective:To evaluate the effect of hematopoietic stem cell transplantation (HSCT) for children with leukemia in our center in recent years. Methods: We retrospectively analyzed data of 87 patients with leukemia underwent HSCT at a median age of 8 years from February 2006 to December 2013 in our center. The median follow-up time was 28 months (range, 2-96), the ratio of male to female patients was 59:28. Conditioning regimen included cyclophosphamide, fludarabine, busulfan with or without (w/o) thiotepa. Anti-thymocyte globulin and cytarabine were individually used for the patients with lymphoid leukemia and myeloid leukemia. GVHD prophylaxis included tacrolimus, mycophenolate mofetil w/o post-transplant cyclophosphamide. Median nucleated cells: 3.75 (1.16`7.56) × 107/Kg. Patients with BCR/ABL+ acute lymphoblastic leukemia (ALL) received imatinib before and after transplant over 6 months per each one. Twenty-six patients received transplant from sibling donors, 31 from haploidentical donor, 30 from unrelated donors; Status before transplant were grouped as CR1 (n= 57), CR 2 (n=13), CR 3 (n=1) and NR (n=16). Source of stem cells included PBSC in 40 cases, UCB in 3 cases, BM in 24 cases, BM+PBSC in 9 cases, and mixed stem cells (BM /PBSC+ UCB) in 11 cases. Results: The estimated 5-year overall survival (OS) was 56.8 ± 5.8% in total.Among them, OS was 54.3 ± 8.0% in 45 patients with ALL; 85.7 ± 13.2% in 8 patients with BCR/ABL+ALL; 48.6 ± 8.7% in 37 patients with BCR/ABL-ALL. 32.8 ± 15% in 29 patients with acute myeloid leukemia and 82.5 ± 11.3% in 13 patients with chronic myelogenous leukemia, respectively. Single factor analysis showed there was no significant difference for OS in comparison of BCR/ABL+ALL, BCR/ABL-ALL, AML and CML (P=0.057), but patients with BCR/ABL+ALL had higher OS compared to those with BCR/ABL-ALL (P=0.048) and to AML (P=0.040). In comparison of difference status before transplant, OS were 55.2 ± 11.6%, 54.9 ± 15.6%, 0,and 27.5 ± 11.6% in CR1, CR2, CR3 and NR, respectively (P=0.025). OS was higher in CR1 than NR (P=0.005). When comparing stem cell source, OS was 65.5 ± 8.5%, 0%, 41.7 ± 11.4%, 33.3 ± 15.7%, and 72 ± 17.8% in PBSC, unrelated CB (UCB), BM, BM+PBSC, and BM/PBSC+UCB transplants, respectively (P=0.003); PBSC transplant associated with higher OS than BM (P=0.049) and BM+PBSC (P=0.009); and BM/PBSC+UCB mixed transplant had highest OS (P=0.026). Multivariate analysis showed Risk factors for OS only remained stem cell source (P=0.046) and status before transplantation (P=0.048). the transplant types (P=0.023), and follow up time(P=0.017). Conclusion: Comparing with data reported in literature we have similar outcomesin total for childhood with leukemia. Use of imatinib pre-/post-transplant for patients with BCR/ABL+ALL conduces to the highest OS in current study. Stem cell sources and the status before transplant have a significant effect on OS. Disclosures No relevant conflicts of interest to declare.

Early lymphocyte recovery (ELR) impact on disease outcome following autologous hematopoietic stem cell transplantation (HDT/ASCT) for multiple myeloma (MM) in the era of novel agents.

2013 ◽  
Vol 31 (15_suppl) ◽  
pp. e19539-e19539
Author(s):  
Jeremy Scott McDuffie ◽  
Bipin N. Savani ◽  
Wichai Chinratanalab ◽  
Stacey Goodman ◽  
John P. Greer ◽  
...  
Keyword(s):  
Minimal Residual Disease ◽  
Residual Disease ◽  
Disease Status ◽  
Novel Agents ◽  
Disease Outcome ◽  
Disease Stage ◽  
Response Criteria ◽  
Hematopoietic Stem ◽  
Significant Difference ◽  
Minimal Residual

e19539 Background: Absolute lymphocyte count (ALC) > 500 cells/ µL on day 15 (ELR+) after HDT/ASCT, has been reported to be an independent prognostic indicator, for improved OS and PFS in patients with MM. Novel agents (immunomodulatory drugs (IMiDs) and proteasome inhibitors), mediate there effect through T-cell stimulation, NK cell activation, anti-proliferation, and are now main stay of therapy for MM. We sought to determine their effects on ELR, and correlated to disease outcome. Methods: A retrospective review of all MM patients seen at our institution undergoing HDT/ASCT from January 2008 to December 2012 was performed. Patients were identified from our CIBMTR database. ALC was determined pre-HDT/ASCT (T1), on day15 (T2) and d30 (T3) post-HDC/ASCT. No restrictions on inclusion were made based upon the International Myeloma Working Group response criteria. All had novel agents as part of their initial induction regimen. Disease response was determined by standard clinical and laboratory CIBMTR response criteria, and minimal residual disease status (MRD) by multiparameter flow cytometry. Results: In our study (n= 184), 52/184 patients had ELR+ while 132/184 had ALC < 500 cells/mL (ELR-) at T2. 21% received IMiDs, 33% proteasome inhibitor and 46% combination therapies. 52% of the ELR+ patients were MRD negative (-) at T1, and improved to 74% and 89% at D100, and 1 year post-HDC/ASCT respectively. Similarly 63%, 70%, and 80% of the ELR- patients, were MRD (-) at similar time-points. Chi squared analysis showed no significant difference in rates of MRD (-) based on ELR. ELR also had no impact on disease status as determined by CIBMTR response criteria, or 1 year PFS and OS (p = 0.383), (p = 0.577) respectively. Multivariate analyses, using cox-regression showed no impact of ALC at T1, T2, T3, age, sex, race, cytogenetic risk, or disease stage on disease outcome. Conclusions: Novel agents improve disease control independent of ELR following HDC/ASCT. Understanding their biologic effect on immune-reconstitution will provide a platform for adoptive immunotherapy to better target minimal residual disease.

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