scholarly journals GvHD-free, relapse-free survival after reduced-intensity allogeneic hematopoietic cell transplantation in older patients with myeloid malignancies

2016 ◽  
Vol 51 (12) ◽  
pp. 1642-1643 ◽  
Author(s):  
A Nazha ◽  
L Rybicki ◽  
D Abounader ◽  
B Bolwell ◽  
R Dean ◽  
...  
Keyword(s):  
Cell Transplantation ◽  
Older Patients ◽  
Hematopoietic Cell Transplantation ◽  
Hematopoietic Cell ◽  
Allogeneic Hematopoietic Cell Transplantation ◽  
Relapse Free Survival ◽  
Free Survival ◽  
Myeloid Malignancies ◽  
Reduced Intensity

scholarly journals Factors Predicting Gvhd Free, Relapse Free Survival (GRFS) after Allogeneic Hematopoietic Cell Transplantation; A Multivariable Analysis of 531 Allografts from a Single Center

Blood ◽  
2015 ◽  
Vol 126 (23) ◽  
pp. 2028-2028
Author(s):  
Melhem Solh ◽  
Xu Zhang ◽  
Katelin Connor ◽  
Stacey Brown ◽  
H. Kent Holland ◽  
...  
Keyword(s):  
Cell Transplantation ◽  
Hematopoietic Cell Transplantation ◽  
Disease Risk ◽  
Multivariable Analysis ◽  
Hematopoietic Cell ◽  
Allogeneic Hematopoietic Cell Transplantation ◽  
Relapse Free Survival ◽  
Free Survival ◽  
One Year ◽  
Very High

Abstract The ideal outcome of allogeneic hematopoietic cell transplantation (allo-HCT) is based on survival that is free of morbidity. The most common causes of treatment failure and morbidity after HCT are relapse, GVHD and non-relapse death. A composite endpoint that measures survival free of clinically significant negative events may be a useful way to determine the success of allo-HCT (1). We assessed GVHD and relapse-free survival (GRFS) where the events were acute GVHD grade 3-4, moderate to severe chronic GVHD, relapse or death in 531 consecutive adult patients who received an allo- HCT between 2006 and 2014 at our center. Median follow up of living patients was 46 months (12-123). Patients were treated using standardized supportive care algorithms at our center. Although this was a retrospective analysis, patient characteristics and outcomes including GVHD grading were obtained from our institutional database where they had been prospectively documented. The median age was 52 (18-77) years. 266 (50%) received myeloablative conditioning, and 428 (81%) received PBSC as stem cell source. Donor type was HLA matched related (MRD, n=198, 37%), matched unrelated (MUD, n=205, 39%) and haploidentical using T-replete grafts and post-transplant cyclophosphamide (HIDT, n=128, 24%). 36% of patients had a high/very high Dana farber disease risk index (DRI). The most common indications for transplant were AML (n=197, 37%), MDS/MPS (n=114, 21%), NHL (n=132, 25%) and ALL (n=68, 13%).1 year OS, disease free survival DFS and GRFS were 78%, 64% and 33% respectively. GRFS after MRD, MUD and HIDT was 39%, 27% and 35% respectively, with MRD recipients having a better GRFS than MUD (p=0.004). Regression analysis showed that GRFS at the one year was lower for, patients transplanted before 2011 than those transplanted between 2011 and 2014(27% vs 39%, p=0.0031), high CIBMTR disease risk than low CIBMTR risk (24% vs 39%, p=0.009) and high/very high DRI than low DRI (23% vs 48%, p<0.001). On multivariable analysis, year of transplant before 2011 (HR =1.2, p=0.03), age >= 50 years (HR 1.22, p=0.05), MUD donor (HR 1.3, p=0.004) and high/very high DRI risk (HR 2.05, p<0.001) were all associated with a worse GFRS at one year post HCT. GFRS is an endpoint that is worth investigating in further trials as a marker of successful HCT. These data suggest that GRFS can be predicted by patient age and DRI but not by HCT-CMI. Importantly the GRFS appears to have improved in more recently transplanted patients and MUD donors produce inferior GRFS to MRD whereas haploidentical donors do not. Table 1. Predictors of GRFS at one year N=531 1 year GRFS HR 95% CI P value Year of BMT2005-2010 2011-2014 270 (51%) 261 (49%) 30% 37% 1.00 0.80 25%-35% 32%-43% - 0.03 AgeAge <50 years Age >= 50 years 228 (43%) 303(57%) 37% 31% 1.00 1.22 31%-43% 26%-36% - 0.05 Donor TypeMRD MUD Haplo Haplo vs MUD 198(37%) 205 (39%) 128 (24%) 39% 27% 35% 1.00 1.30 1.13 0.81 33%-45% 22%-33% 27%-42% - 0.004 0.379 0.112 DRILow Intermediate High/very high 78(15%) 258 (49%) 189 (36%) 48% 36% 23% 1.00 1.42 2.05 38%-58% 31%-42% 18%-29% - 0.025 <0.001 1. Holtan SG, DeFor TE, Lazaryan A, Bejanyan N, Arora M, Brunstein CG, et al. Composite end point of graft-versus-host disease-free, relapse-free survival after allogeneic hematopoietic cell transplantation. Blood. 2015;125(8):1333-8. Figure 1. Figure 1. Figure 2. Figure 2. Disclosures No relevant conflicts of interest to declare.

scholarly journals Efficacy of G-CSF Primed DLI Using Cells Reserved at the Time of Harvest in Patients with Hematologic Malignancies Who Lately Relapsed after Allogeneic PBSCT

Blood ◽  
2016 ◽  
Vol 128 (22) ◽  
pp. 5809-5809
Author(s):  
YooJin Lee ◽  
Joon Seok Yoon ◽  
In Hee Lee ◽  
Joon Ho Moon ◽  
Sang Kyun Sohn
Keyword(s):  
Cell Transplantation ◽  
Hematopoietic Cell Transplantation ◽  
Hematologic Malignancies ◽  
Hematopoietic Cell ◽  
Allogeneic Hematopoietic Cell Transplantation ◽  
Late Relapse ◽  
Relapse Free Survival ◽  
Free Survival ◽  
Early Relapse ◽  
Relapse Group

Abstract Introduction There is no standard therapeutic approach for the relapse after allogeneic hematopoietic cell transplantation (allo-HCT). The aim of this paper is to confirm the role of granulocyte colony-stimulating factor (G-CSF) primed donor lymphocyte infusion (DLI) according to the timing of relapse after allo-HCT with limited CD34+ cell dose (<6x106/kg) Methods One hundred ten patients who had relapsed after allo-HCT at Kyungpook National University Hospital from November 2001 to December 2014, including 40 patients who received DLI from cryopreserved cells derived from the original G-CSF primed graft, were retrospectively reviewed. The patients were classified into early relapse or late relapse group by the median time of relapse after transplant. Results The median age at transplant was 38.5 years (range, 17-67 years) and male was 69 patients (62.2%). Primary diseases for allo-HCT included AML/MDS (n=63, 57.3%), ALL (n=32, 29.1%), CML (n=8, 7.3%), and NHL (n=7, 6.4%). Fifty four patients (49.1%) were in CR1 (complete remission), 16 (14.5%) in CR2, and 40 (36.4%) in relapsed and refractory status at the time of HCT. Sixty nine patients (62.2%) received myeloablative conditioning regimen. The median dose of CD34+ cells was 5.06x106/kg (range, 1~20.6x106/kg). Ninety nine percent of patients achieved the neutrophil recovery (> 500x103/mm3 for 3 days) at a median time of 13 days (range 9-24 days). The median time from HCT to relapse was 139 days (range, 21~1801 days). The median relapse free survival (RFS) since HCT was not significantly different according to the dose of CD34+ cells: median 147 days (range, 122-171) and 157 days (range, 87-227) in CD34+ < 6x106/kg and > 6x106/kg, respectively (p=0.249). The median overall survival (OS) since HCT was not significantly different according to the dose of CD34+ cells: median 324 days (range, 272-375) and 262 days (range, 235-288) in CD34+ < 5.06x106/kg and > 5.06x106/kg, respectively (p=0.554).The incidence of chronic GVHD was more frequent in higher CD34+ group (32.9% vs. 48.2%, P=0.042). After relapse, 57 patients (51.8%) were treated with salvage chemotherapy, 13 patients (11.8%) with second allo-HCT, and 40 patients (36.4%) with G-CSF primed DLI. The median number of CD3+T cell was 2.95x107/kg (range, 0.1~5.43x107/kg). Fourteen patients (23.6%) achieved DLI-induced CR, 20 patients progressed, and 6 patients were not evaluable for response. DLI-induced acute GVHD was observed in 25 patients (62.5%) and chronic GVHD developed in 4 patients (10%). The 1-year overall survival (OS) since relapse was not significantly different according to the use of DLI in early relapse group (11.7 +/- 5.3% and 10.0 +/- 6.7%, p=0.663), but in late relapse group, significantly higher in DLI than non-DLI (43.3 +/- 11.3% and 17.1 +/- 6.9%, p=0.021). The patients treated with DLI showed significantly higher RFS in late relapse group (286 days vs. 165 days, p=0.004). The incidence of DLI-induced GVHD did not differ between two groups. Conclusions G-CSF primed DLI after allo-HCT with limited CD34+ cell dose can be feasible and effective option in terms of response, donor convenience and its cost. In the late relapse group, it may replace the second transplantation for the patients with hematologic malignancies lately relapsed after first allo-HCT. Figure 1 Relapse free survival according to DLI use, (A) RFS in patients experiencing early relapse of hematologic malignancies after allogeneic hematopoietic cell transplantation (B) RFS in patients experiencing late relapse of hematologic malignancies after allogeneic hematopoietic cell transplantation, DLI- donor lymphocyte infusion; RFS- Relapse free survival Figure 1. Relapse free survival according to DLI use, (A) RFS in patients experiencing early relapse of hematologic malignancies after allogeneic hematopoietic cell transplantation (B) RFS in patients experiencing late relapse of hematologic malignancies after allogeneic hematopoietic cell transplantation, DLI- donor lymphocyte infusion; RFS- Relapse free survival Figure 2 Figure 2. Disclosures No relevant conflicts of interest to declare.

scholarly journals Poor Outcomes of HLA-Mismatched Allogeneic Hematopoietic Cell Transplantation and High Ferritin Levels after a Reduced-Intensity Conditioning Regimen in Patients with Advanced Myelofibrosis

Blood ◽  
2019 ◽  
Vol 134 (Supplement_1) ◽  
pp. 5742-5742
Author(s):  
Han Bi Lee ◽  
Jae-Ho Yoon ◽  
Gi June Min ◽  
Sung-Soo Park ◽  
Silvia Park ◽  
...  
Keyword(s):  
Board Of Directors ◽  
Cell Transplantation ◽  
Research Funding ◽  
Acute Gvhd ◽  
Hematopoietic Cell Transplantation ◽  
Hematopoietic Cell ◽  
Allogeneic Hematopoietic Cell Transplantation ◽  
Reduced Intensity Conditioning ◽  
Advisory Committees ◽  
Reduced Intensity

Allogeneic hematopoietic cell transplantation (allo-HCT) preconditioning intensity, donor choice, and graft-versus-host disease (GVHD) prophylaxis for advanced myelofibrosis (MF) have not been fully elucidated. Thirty-five patients with advanced MF were treated with reduced-intensity conditioning (RIC) allo-HCT. We searched for matched sibling (n=16) followed by matched (n=10) or mismatched (n=5) unrelated and familial mismatched donors (n=4). Preconditioning regimen consisted of fludarabine (total 150 mg/m2) and busulfan (total 6.4 mg/kg) with total body irradiation≤ 400cGy. All showed engraftments, but four (11.4%) showed either leukemic relapse (n=3) or delayed graft failure (n=1). Two-year overall survival (OS) and non-relapse mortality (NRM) was 60.0% and 29.9%, respectively. Acute GVHD was observed in 19 patients, and grade III-IV acute GVHD was higher with HLA-mismatch (70% vs. 20%, p=0.008). Significant hepatic GVHD was observed in nine patients (5 acute, 4 chronic), and six of them died. Multivariate analysis revealed inferior OS with HLA-mismatch (HR=6.40, 95%CI 1.6-25.7, p=0.009) and in patients with high ferritin level at post-HCT D+21 (HR=7.22, 95%CI 1.9-27.5, p=0.004), which were related to hepatic GVHD and high NRM. RIC allo-HCT can be a valid choice for advanced MF. However, HLA-mismatch and high post-HCT ferritin levels related to significant hepatic GVHD should be regarded as poor-risk parameters. Disclosures Kim: Handok: Honoraria; Amgen: Honoraria; Celgene: Consultancy, Honoraria; Astellas: Consultancy, Honoraria; Hanmi: Consultancy, Honoraria; AGP: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; SL VaxiGen: Consultancy, Honoraria; Novartis: Consultancy; Janssen: Honoraria; Daiichi Sankyo: Honoraria, Membership on an entity's Board of Directors or advisory committees; Otsuka: Honoraria; BL & H: Research Funding; Chugai: Honoraria; Yuhan: Honoraria; Sanofi-Genzyme: Honoraria, Research Funding; Novartis: Honoraria, Membership on an entity's Board of Directors or advisory committees. Lee:Alexion: Consultancy, Honoraria, Research Funding; Achillion: Research Funding.

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