scholarly journals Higher Total Nucleated Cell Dose, but Not CD3+, 4+, 8+, or 34+ Cell Dose, Is Associated with Better Overall and Progression-Free Survival after Allogeneic Peripheral Blood Hematopoietic Cell Transplantation (AlloPBHCT) with TBI-Based Conditioning Regimens

2014 ◽  
Vol 20 (2) ◽  
pp. S30-S31
Author(s):  
Michael Burns ◽  
Anurag Singh ◽  
Yali Zhang ◽  
George L. Chen ◽  
Hong Liu ◽  
...  
Keyword(s):  
Cell Transplantation ◽  
Peripheral Blood ◽  
Hematopoietic Cell Transplantation ◽  
Progression Free Survival ◽  
Hematopoietic Cell ◽  
Free Survival ◽  
Cell Dose ◽  
Conditioning Regimens

scholarly journals Improved Outcomes After Autologous Hematopoietic Cell Transplantation for Light Chain Amyloidosis: A Center for International Blood and Marrow Transplant Research Study

2015 ◽  
Vol 33 (32) ◽  
pp. 3741-3749 ◽  
Author(s):  
Anita D'Souza ◽  
Angela Dispenzieri ◽  
Baldeep Wirk ◽  
Mei-Jie Zhang ◽  
Jiaxing Huang ◽  
...  
Keyword(s):  
Cell Transplantation ◽  
Light Chain ◽  
Hematopoietic Cell Transplantation ◽  
Progression Free Survival ◽  
Marrow Transplant ◽  
Hematopoietic Cell ◽  
Post Transplantation ◽  
Free Survival ◽  
Blood And Marrow Transplant ◽  
Autologous Hematopoietic Cell Transplantation

Purpose Autologous hematopoietic cell transplantation, or autotransplantation, is effective in light-chain amyloidosis (AL), but it is associated with a high risk of early mortality (EM). In a multicenter randomized comparison against oral chemotherapy, autotransplantation was associated with 24% EM. We analyzed trends in outcomes after autologous hematopoietic cell transplantation for AL in North America. Patients and Methods Between 1995 and 2012, 1,536 patients with AL who underwent autotransplantation at 134 centers were identified in the Center for International Blood and Marrow Transplant Research database. EM and overall survival (OS) were analyzed in three time cohorts: 1995 to 2000 (n = 140), 2001 to 2006 (n = 596), and 2007 to 2012 (n = 800). Hematologic and renal responses and factors associated with EM, relapse and/or progression, progression-free survival and OS were analyzed in more recent subgroups from 2001 to 2006 (n = 197) and from 2007 to 2012 (n = 157). Results Mortality at 30 and 100 days progressively declined over successive time periods from 11% and 20%, respectively, in 1995 to 2000 to 5% and 11%, respectively, in 2001 to 2006, and to 3% and 5%, respectively, in 2007 to 2012. Correspondingly, 5-year OS improved from 55% in 1995 to 2000 to 61% in 2001 to 2006 and to 77% in 2007 to 2012. Hematologic response to transplantation improved in the latest cohort. Renal response rate was 32%. Centers performing more than four AL transplantations per year had superior survival outcomes. In the multivariable analysis, cardiac AL was associated with high EM and inferior progression-free survival and OS. Autotransplantation in 2007 to 2012 and use of higher dosages of melphalan were associated with a lowered relapse risk. A Karnofsky score less than 80 and creatinine levels 2 mg/m2 or greater were associated with worsened OS. Conclusion Post-transplantation survival in AL has improved, with a dramatic reduction in early post-transplantation mortality and excellent 5-year survival. The risk-benefit ratio for autotransplantation has changed, and randomized comparison with nontransplantation approaches is again warranted.

scholarly journals Outcomes after allogeneic hematopoietic cell transplantation with nonmyeloablative or myeloablative conditioning regimens for treatment of lymphoma and chronic lymphocytic leukemia

Blood ◽  
2008 ◽  
Vol 111 (1) ◽  
pp. 446-452 ◽  
Author(s):  
Mohamed L. Sorror ◽  
Barry E. Storer ◽  
David G. Maloney ◽  
Brenda M. Sandmaier ◽  
Paul J. Martin ◽  
...  
Keyword(s):  
Chronic Lymphocytic Leukemia ◽  
Cell Transplantation ◽  
Hematopoietic Cell Transplantation ◽  
Previous Treatment ◽  
Progression Free Survival ◽  
Lymphocytic Leukemia ◽  
Hematopoietic Cell ◽  
Free Survival ◽  
P 75 ◽  
Conditioning Intensity

Allogeneic conventional hematopoietic cell transplantation (HCT) can be curative treatment for lymphoid malignancies, but it has been characterized by high nonrelapse mortality (NRM). Here, we compared outcomes among patients with lymphoma or chronic lymphocytic leukemia given either nonmyeloablative (n = 152) or myeloablative (n = 68) conditioning. Outcomes were stratified by the HCT-specific comorbidity index. Patients in the nonmyeloablative group were older, had more previous treatment and more comorbidities, more frequently had unrelated donors, and more often had malignancy in remission compared with patients in the myeloablative group. Patients with indolent versus aggressive malignancies were equally distributed among both cohorts. After HCT, patients without comorbidities both in the nonmyeloablative and myeloablative cohorts had comparable NRM (P = .74), overall survival (P = .75), and progression-free survival (P = .40). No significant differences were observed (P = .91, P = .89, and P = .40, respectively) after adjustment for pretransplantation variables. Patients with comorbidities experienced lower NRM (P = .009) and better survival (P = .04) after nonmyeloablative conditioning. These differences became more significant (P < .001 and .007, respectively) after adjustment for other variables. Further, nonmyeloablative patients with comorbidities had favorable adjusted progression-free survival (P = .01). Patients without comorbidities could be enrolled in prospective randomized studies comparing different conditioning intensities. Younger patients with comorbidities might benefit from reduced conditioning intensity.

Reduced Intensity Hematopoietic Cell Transplantation in Active Disease AML Is Associated with Leukemia Free Survival and Relapse Comparable to Myeloablative Conditioning

Blood ◽  
2016 ◽  
Vol 128 (22) ◽  
pp. 3477-3477
Author(s):  
Se young Han ◽  
Rizwan Romee ◽  
Michael Slade ◽  
Pavan Kumar Bhamidipati ◽  
John F DiPersio ◽  
...  
Keyword(s):  
Cell Transplantation ◽  
Research Funding ◽  
Hematopoietic Cell Transplantation ◽  
Hematopoietic Cell ◽  
Free Survival ◽  
Conditioning Regimens ◽  
Active Disease ◽  
Reduced Intensity

Abstract Introduction: Up to 40% of new acute myeloid leukemia (AML) patients fail to achieve complete remission (CR), and a significant number of patients achieving remission eventually relapse. Allogeneic hematopoietic cell transplantation (allo-HCT) remains the best curative option for these patients with a long-term leukemia free survival (LFS) of around 20-30% with the use of intensive myeloablative condition (MAC) transplants. Active disease AML patients otherwise deemed unfit for MAC regimens have limited treatment options. Although reduced intensity condition (RIC) has broadened transplant eligibility in the elderly AML patients particularly in CR, there is a paucity of data on the use RIC allo-HCT in AML patients with active disease. To answer this question, we retrospectively analyzed data from active disease AML patients who underwent RIC allo-HCT and compared their outcomes with contemporaneous patients who underwent MAC allo-HCT at our institution. Patients and methods: Our cohort included all patients with active disease AML (primary induction failure, relapsed refractory or cytogenetic persistence) at the time of transplantation, who underwent allo-HCT at Washington University Medical Center in St. Louis between January 2006 and June 2015. Patients were classified according to the intensity of conditioning regimens: MAC versus RIC. The primary study endpoints were leukemia free survival (LFS) and overall survival (OS). LFS was defined as the time from the achievement of CR after allo-HCT to the time of relapse, death in remission, or last follow-up. OS was defined as the time from transplantation to the time of death from any cause or last follow-up. The between-group differences in LFS and OS were described using Kaplan-Meier (KM) survival curves and compared by log-rank test. Univariate Cox regression analysis for LFS was performed. All analyses were two-sided, and significance was set at a p-value of 0.05, using SAS 9.4 (SAS Institutes, Cary, NC). Results: 138 patients were included. 30 patients (21.7%) underwent RIC allo-HCT and 108 (78.3%) underwent MAC allo-HCT. Their baseline characteristics are listed in Table 1. 21 patients (72.4%) in RIC and 77 (81.9%) in MAC achieved CR on day-28 bone marrow biopsy. Notably, there were 16 patients (1 RIC and 15 MAC) who died prematurely without post-transplant evaluation; subsequently they were excluded from LFS, relapse and NRM calculations. There was no difference in the LFS in these two groups; 1-year and 3-year LFS were 40.6% (95% CI 23-70) and 33.1% (95% CI 17-66) in the RIC patients while 40.7% (95% CI 31-54) and 33.2% (95% CI 23-47) in the MAC patients, respectively (p=0.99) (Figure 1A). Similarly the CI of relapse at 1 year and 3 year was not different in the two groups; 45.8% (95% CI 30-71) and 50.5% (95% CI 33-76) in RIC group vs. 51.9% (95% CI 43-63) and 56.8% (95% CI 48-67) in MAC group, respectively (p=0.61) (Figure 1B). The CI of NRM at 1-year and 3-year was 28.1% (95% CI 16-50) and 32.6% (95% CI 19-56) in RIC group compared to 17.9% (95% CI 11-28) and 21.0% (95% CI 14-31) in the MAC group (p = 0.21). However, OS in both groups remained poor with 1-year and 3-year OS of 25.1% (95% CI 14-44) and 13.2% (95% CI 6-31) in RIC vs. 35.5% (95% CI 28-46) and 22.0% (95% CI 15-32) in MAC, respectively (p = 0.21). On univariate analysis for LFS and relapse, only cGvHD was associated with higher LFS (p<0.01, HR 0.27, 95% HR 0.13-0.52) and lower relapse risk (p= 0.01, HR 0.37, 95% HR 0.15-0.89) in these patients. On multivariate analysis for LFS, only cGvHD was statistically significant (p<0.01, HR 0.32, 95% HR 0.18-0.56). On the other hand, intermediate cytogenetic risk (p=0.01, HR 1.59, 95% HR 1.08-2.34) and cGvHD (p<0.01, HR 0.12, 95% HR 0.05-0.27) were significant for OS. Conclusion: The use of RIC allo-HCT in active disease AML is associated with LFS and relapse comparable to MAC allo-HCT. However, high relapse rates and NRM, in both groups translated into poor long term OS. Careful selection of patients and early utilization of transplant without subjecting these patients to multiple salvage regimens might help lower NRM rates in future studies. Notably, our study might open a window for future prospective studies aimed at finding improved ways to harness the graft versus leukemia (GvL) effect associated with RIC transplantation in patients who are otherwise not able to tolerate more toxic intensive conditioning regimens. LFS LFS Figure 1 Relapse Figure 1. Relapse Figure 2 Figure 2. Disclosures DiPersio: Incyte Corporation: Research Funding. Vij:Karyopharm: Honoraria; Janssen: Honoraria; Bristol-Myers Squibb: Honoraria; Novartis: Honoraria; Amgen: Honoraria, Research Funding; Celgene: Consultancy; Takeda: Honoraria, Research Funding.

scholarly journals Increased Early Mortality After Fludarabine and Melphalan Conditioning with Peripheral Blood Grafts in Haploidentical Hematopoietic Cell Transplantation with Post-Transplant Cyclophosphamide

2021 ◽  
Author(s):  
Luke Eastburg ◽  
David Russler-Germain ◽  
John DiPersio ◽  
Thomas Fountaine ◽  
Jeffrey Andolina ◽  
...  
Keyword(s):  
Cell Transplantation ◽  
Peripheral Blood ◽  
Hematopoietic Cell Transplantation ◽  
Disease Free Survival ◽  
Hematopoietic Cell ◽  
High Rate ◽  
Cell Transplant ◽  
Post Transplant ◽  
Conditioning Regimens ◽  
Haploidentical Hematopoietic Cell Transplantation

Abstract Due to the evolving use of haploidentical donor grafts in hematopoietic cell transplantation, there is increased need to better understand the risks and benefits of using bone marrow versus peripheral blood grafts, as well as how specific pre-transplantation conditioning regimens impact patient safety and treatment outcomes. We performed a retrospective analysis of 38 patients at two centers who specifically underwent haploidentical hematopoietic cell transplantation using fludarabine plus melphalan-based conditioning regimens with post-transplant cyclophosphamide and peripheral blood donor grafts. We observed an unexpectedly high rate of early non-relapse mortality of 21% at 100 days and 34% at 1-year. In addition, 40% of all patients suffered from severe cytokine release syndrome and 45% of all patients suffered from kidney injury, often necessitating renal replacement therapy. The poor outcomes with 1-year overall survival of 34%, disease-free survival of 29%, and non-relapse mortality of 34% motivate us to reconsider the appropriateness of the combination of fludarabine and melphalan conditioning with T-cell replete peripheral blood grafts in the setting of haploidentical hematopoietic cell transplant with post-transplant cyclophosphamide.

scholarly journals Reversal of Low Donor Chimerism Following Hematopoietic Cell Transplantation Using Pentostatin and Donor Lymphocyte Infusion

Blood ◽  
2016 ◽  
Vol 128 (22) ◽  
pp. 2215-2215
Author(s):  
Merav Bar ◽  
Mary Flowers ◽  
Barry E. Storer ◽  
Thomas R. Chauncey ◽  
Michael A Pulsipher ◽  
...  
Keyword(s):  
Cell Transplantation ◽  
Hematopoietic Cell Transplantation ◽  
Progression Free Survival ◽  
Donor Lymphocyte Infusion ◽  
Advisory Board ◽  
Hematopoietic Cell ◽  
Free Survival ◽  
Donor Chimerism ◽  
Increased Risk ◽  
Grade Ii

Abstract Objectives: Low donor chimerism after hematopoietic cell transplantation (HCT) is associated with increased risk of post transplant relapse. Our group has shown that donor lymphocyte infusion (DLI) was ineffective for converting <40% donor CD3 chimerism to full donor chimerism. If successful, however, donor CD3 chimerism >90% elicited GVT effects (Blood 2004;103:790). To facilitate effectiveness of DLI for patients (pts) with low or declining donor CD3chimerism, a prospective multicenter trial assessing the safety and efficacy of addingpentostatin was developed. Patients and Methods: Pts at risk for rejection after HCTs, defined as low (<50%) but persistent (>5%) donor CD3 chimerism and with stable/in remission disease, were included. Pts were excluded if they had evidence of relapse/progression, ongoing grades II-IV acute (a)GVHD, or extensive chronic (ec)GVHD. Between 2003 and 2014, 36 pts were treated on the study; 35 pts received a total of 41 DLIs following a dose of pentostatin, and 1 pt received pentostatin only. Diagnoses included AML (n=13), NHL (n=4), CLL (n=7), CML (n=2), MDS (n=6), MPD (n=2), MM (n=1), NHL and MDS (n=1). Pts received nonmyeloablative (n= 35) or ablative (n=1) conditioning, followed by PBSCs from HLA-matched related (n=17) or unrelated (n=17) donors, or 1-allele mismatched unrelated donor (n=2). Median age at HCT was 58 (34-72) years. DLI was given at a median of 96 (54-339) days after HCT. A dose of pentostatin was given 2 days before infusing 1x107 CD3 cells/kg (n=26), 2x107 CD3 cells/kg (n=1), or 3x107 CD3 cells/kg (n=14). Per protocol, prophylactic immunosuppression (IS) with cyclosporine and MMF was given after DLI to the last 6 pts on study. Results: Median donor CD3chimerism beforepentostatin/DLI was 28 (5-47)%. Efficacy, defined by increases in donor CD3chimerism>10% maintained to day 56 post-DLI, was seen in 16 pts (44.4%) with a median CD3 donorchimerism of 64 (48-100)%. There was a trend for better efficacy among the 21 pts who received first treatment within 100 days after transplant (57%) compared to the 15 pts who received first treatment more than 100 days after HCT (27%) (p=0.07). Six pts received 2nd treatment ofpentostatin/DLI; among them 1 responded. Fifteen pts (12 responders) developedaGVHD after DLI [grade I (n=2), II (n=9), III (n=3), IV (n=1)] at a median of 10 (0-83) days after DLI. One pt developed skinGVHD, grade II, afterpentostatin administration and DLI was aborted. Of the 16 pts who developedaGVHD afterpentostatin/DLI, 3 had a prior history of GVHD after transplant. Thirteen pts developedcGVHD, ofwhom 10 developedecGVHD at a median of 112 (13-347) days after DLI. One pt developedecGVHD with no prioraGVHD. Among the 6 pts who received prophylaxis IS after DLI 1 pt developedaGVHD grade II, and none developedcGVHD. However, only 2 of those 6 pts responded. Seventeen pts developed grade 4cytopenia after DLI; 9 pts developed both neutropenia and thrombocytopenia, 4 pts developed neutropenia, and 4 pts developed thrombocytopenia. Among the 13 patients who developed grade 4 neutropenia, 9 (69%) were non-responders. Median time between DLI and lowest ANC count was 22 (2-100) days, and neutropenia lasted for median of 7 (1-52) days. Twelve pts received platelet transfusions started at median of 33 (1-98) days after DLI. Nineteen pts relapsed at a median of 91 (26-777) days after DLI. Among the 20 non-responders 12 relapsed (60%), compared to 7 of 16 responders (44%) (HR 0.64 (0.3-1.6), p=0.35). Ten of the 17 pts (59%) who developedcytopenia relapsed, 6 ofwhom (60%) were non-responders. Median number of significant infections was 2 (0-10) per pt. Twenty-eight pts died at a median of 522 (67-2028) days after DLI. Causes of death were relapse (n=21), respiratory failure/infections (n=4), grade IV GVHD (n=2), or other causes (n=1). Five of the 16 responders (31%) are alive, all in CR. Six of the 20 non-responders (30%) are alive, only 3 in CR (Figure 1). Summary:Pentostatin/DLI increased donor CD3chimerism in pts after HCT if was given within 100 days after transplant, and it was well tolerated. Response was associated with GVHD. Delayed treatment after HCT and prophylactic IS after DLI were associated with decreased efficacy. There was a trend for higher relapse rate among the non-responders and pts who developed cytopenia, but the differences were not statistically significant. Figure Progression Free Survival after pentostatin/DLI Figure. Progression Free Survival after pentostatin/DLI Disclosures Pulsipher: Novartis: Consultancy, Other: Advisory Board, Steering Committee for Phase II Study; Jazz Pharmaceutical: Consultancy, Other: Advisory Board; Chimerix: Consultancy, Other: Advisory Board ; Medac: Other: Travel support for a study group.

Does Allogeneic Hematopoietic Cell Transplantation Benefit Older (≥ 60) AML/MDS Patients With Monosomal Karyotype?

Blood ◽  
2013 ◽  
Vol 122 (21) ◽  
pp. 3399-3399
Author(s):  
James L Slack ◽  
Nandita Khera ◽  
Veena Fauble ◽  
Jose F Leis ◽  
Lisa Sproat ◽  
...  
Keyword(s):  
Cell Transplantation ◽  
Research Funding ◽  
Hematopoietic Cell Transplantation ◽  
Progression Free Survival ◽  
Hematopoietic Cell ◽  
Allogeneic Hematopoietic Cell Transplantation ◽  
Structural Abnormality ◽  
Free Survival ◽  
The Impact ◽  
Monosomal Karyotype

Abstract Background The prognosis for AML or MDS patients (pts) with monosomal karyotype (MK) is dismal. Although a benefit for allogeneic hematopoietic cell transplantation (allo-HCT) compared to chemotherapy or autologous HCT has been demonstrated in young (≤ 60) pts (Cornelissen, 2012), the curative potential of allo-HCT in older (≥ 60) pts with monosomal karyotype AML/MDS is not known. Patients and methods In this retrospective review, we analyzed outcomes for 69 AML (n = 49) or MDS (n = 20) pts ≥ 60 who underwent allo-HCT at Mayo Clinic Arizona between 2005 and 2013, based on cytogenetic grouping as follows: cytogenetically normal (CN, n = 23), cytogenetically abnormal but not MK (CA, n = 32), and MK (n = 14). Monosomal karyotype was defined (Breems, 2008) as a karyotype with at least two autosomal monosomies or a single autosomal monosomy in combination with at least one structural abnormality. Univariate and multivariate statistical analyses were performed to evaluate the impact of these 3 cytogenetic groupings on outcome (primary endpoint progression-free survival). The median age for all pts was 66 (60-76), and median follow-up for surviving pts was 22 months (range 70 days – 7.1 years). Thirty-seven pts had high-risk disease (MDS > 5% blasts or AML not in CR), while 32 were considered standard risk (MDS <5% blasts or AML in CR). The majority of pts had good performance status (KPS ≥ 90% in 66), but 34 pts (49%) had an HCT-CI score of ≥ 3. Conditioning was myeloablative (Bu-Cy) in 4, reduced toxicity FBM (Fludarabine, BCNU, Melphalan) in 36, and RIC/NMA in 29. Donors were matched related in 18, matched unrelated in 36, and mismatched unrelated in 15. GVHD prophylaxis included tacrolimus in all pts combined with mycophenolate mofetil (37) or methotrexate (32); 49 pts received in-vivo T-cell depletion with rabbit anti-thymocyte globulin (rATG, Thymoglobulin, Genzyme, Cambridge, MA). Results The Kaplan-Meier estimate of progression-free survival (PFS) at 2 yrs was 59% (CN), 39% (CA), and 1.5% (MK); P = 0.004 (Fig. 1). The cumulative incidence of relapse at 2 yrs (with death without relapse as a competing risk) was 34% (CN), 25% (CA), and 94% (MK); P= 0.009). In a Cox proportional hazards analysis adjusted for age (≤ 66 vs. > 66), risk status (standard vs. high), conditioning (myeloablative [Bu-Cy + FBM] vs. RIC/NMA), use of ATG (yes/no), donor type (unrelated vs. related), and HCT-CI (0-2 vs. ≥ 3), the only factor predictive for inferior PFS was cytogenetic status (MK vs. CN, HR 4.64 [95% CI, 1.7 – 13]; P = 0.003); (MK vs. CA, HR 2.4 [95% CI 0.97 – 5.9]; P = .057). Conclusions Standard allo-HCT in AML or MDS pts ≥ 60 with a monosomal karyotype appears to have limited curative potential. Although larger studies will be required to confirm our results, novel transplant approaches or post-transplant strategies to prevent relapse should be a focus of future studies in this incurable pt population. Disclosures: Reeder: Novartis: Research Funding; Celgene: Research Funding; Millennium: Research Funding.

Sign in / Sign up

Export Citation Format

Share Document