scholarly journals Donor Natural Killer (NK) Cell Immunotherapy Following Non-Myeloablative HLA-Haploidentical Hematopoietic Cell Transplantation (HCT) Improves Relapse and Progression Free Survival (PFS) in Patients with Hematologic Malignancies

2016 ◽  
Vol 22 (3) ◽  
pp. S43-S44 ◽  
Author(s):  
Monica Thakar ◽  
Parameswaran N. Hari ◽  
Carolyn A. Keever-Taylor ◽  
Lori Jones ◽  
Shelly Heimfeld ◽  
...  
Keyword(s):  
Natural Killer ◽  
Cell Transplantation ◽  
Hematopoietic Cell Transplantation ◽  
Nk Cell ◽  
Progression Free Survival ◽  
Hematologic Malignancies ◽  
Hematopoietic Cell ◽  
Free Survival ◽  
Cell Immunotherapy ◽  
Haploidentical Hematopoietic Cell Transplantation

scholarly journals HLA-haploidentical vs matched-sibling hematopoietic cell transplantation: a systematic review and meta-analysis

2019 ◽  
Vol 3 (17) ◽  
pp. 2581-2585 ◽  
Author(s):  
Mohamad A. Meybodi ◽  
Wenhao Cao ◽  
Leo Luznik ◽  
Asad Bashey ◽  
Xu Zhang ◽  
...  
Keyword(s):  
Systematic Review ◽  
Cell Transplantation ◽  
Hematopoietic Cell Transplantation ◽  
Meta Analysis ◽  
Hematopoietic Cell ◽  
Free Survival ◽  
Relative Contribution ◽  
Haploidentical Hematopoietic Cell Transplantation ◽  
Matched Sibling ◽  
Outcome Differences

Abstract HLA haploidentical hematopoietic cell transplantation (haplo-HCT) using posttransplantation cyclophosphamide (PT-Cy) is an alternative strategy when a matched sibling donor (MSD) is not available. We performed a systematic review and meta-analysis to compare the outcomes of MSD vs haplo-HCT. Eleven studies (1410 haplo-HCT and 6396 MSD recipients) were meta-analyzed. All studies were retrospective and high quality, and 9 were multicenter. Haplo-HCT was associated with ~50% lower risk of chronic graft-versus-host disease (GVHD) (hazard ratio [HR], 0.55; 95% confidence interval [CI], 0.41-0.74), but higher risk of nonrelapse mortality (HR, 1.36; 95% CI, 1.12-1.66). Relapse, survival, acute GVHD, and GVHD-free relapse-free survival were not significantly different between the groups. Deciphering the relative contribution of PT-Cy and HLA disparity to the observed outcome differences between the groups requires further research.

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.

scholarly journals Donor Age Determines Outcome in Acute Leukemia Patients Undergoing Haploidentical Hematopoietic Cell Transplantation

Blood ◽  
2017 ◽  
Vol 130 (Suppl_1) ◽  
pp. 850-850
Author(s):  
Jonathan Canaani ◽  
Bipin N. Savani ◽  
Myriam Labopin ◽  
Xiao Jun Huang ◽  
Fabio Ciceri ◽  
...  
Keyword(s):  
Multivariate Analysis ◽  
Acute Leukemia ◽  
Cell Transplantation ◽  
Hematopoietic Cell Transplantation ◽  
Hematopoietic Cell ◽  
Donor Selection ◽  
Donor Age ◽  
Free Survival ◽  
Haploidentical Hematopoietic Cell Transplantation ◽  
The Impact

Abstract Introduction Haploidentical hematopoietic cell transplantation (haplo-HCT) is being increasingly used in acute leukemia patients as an alternative transplant modality when matched sibling or matched unrelated donors are unavailable. As several potential haploidentical relative donors are typically available for a given patient, optimizing donor selection to improve clinical outcome is crucial. The impact of donor age and kinship on the outcome of acute leukemia patients is not clearly established in this setting. Patients and methods Using the multinational registry of the acute leukemia working party of the European society for blood and marrow transplantation we retrospectively analyzed the clinical outcomes of adult acute myeloid leukemia (AML) and acute lymphoblastic leukemia (ALL) patients who underwent a first T-cell replete related haplo-HCT between 2005 and 2015. Results Our cohort comprised 1270 patients of which 1019 had AML and 251 had ALL. Seven hundred patients were transplanted at age 40 or over and 570 were transplanted at an age of less than 40. Median follow-up for patients in this analysis was 27 months (range 0.6-119 months). In multivariate analysis, patients over the age of 40 were significantly affected by increasing donor age resulting in higher non-relapse mortality (NRM) [Hazard ratio (HR)=1.86, confidence interval (CI) 95%, 1.18-2.94; P=0.007], inferior leukemia-free survival (LFS) (HR=1.59, CI 95%, 1.13-2.24; P=0.007), overall survival (OS) (HR=1.74, CI 95%, 1.22-2.47; P=0.002), and GVHD-free/relapse-free survival (GRFS) (HR=1.6, CI 95%, 1.16-2.22; P=0.004) rates when donors were over the age of 40. Whereas the relationship of the donor to the patient, namely sibling versus child donor, did not impact on patient outcome in a statistically significant manner, our results indicated that in the group of patients over 40 who were transplanted from their children, outcomes were less favorable when donors were over the age of 35. Specifically, this patient subset experienced an increased rate of NRM (HR=1.82, CI 95%, 1.13-2.9; P=0.01), inferior LFS (HR=1.5, CI 95%, 1.05-2.13; P=0.03) as well as inferior OS (HR=1.5, CI 95%, 1.04-2.15; P=0.03). For patients younger than 40 years of age, multivariate analysis revealed that having a donor over the age of 55 was independently associated with a decreased risk for extensive chronic GVHD (HR=0.16, CI 95%, 0.02-0.95; P=0.044) concomitant with a trend for an increased risk of relapse (HR=1.85, CI 95%, 0.97-3.49; P=0.058). The rates of NRM, OS, LFS, acute GVHD, and GRFS were not significantly impacted by donor age in this age group. Conclusions Our data establish donor age and kinship as significant determinants of outcome following haplo-HCT for acute leukemia patients with potential implications for future donor selection algorithms in haplo-HCT. Disclosures Savani: Jazz Pharmaceuticals: Speakers Bureau. Ciceri: GSK: Other: B-thalassemia gene therapy was developed by Fondazione Telethon and Ospedale San Raffaele and has been inlicenced by GSK that provides funding for the clinical trial, Research Funding. Mohty: Sanofi: Honoraria, Speakers Bureau.

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.

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