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 ◽  
...  

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.

Blood ◽  
2021 ◽  
Vol 138 (Supplement 1) ◽  
pp. 912-912
Author(s):  
Guru Subramanian Guru Murthy ◽  
Soyoung Kim ◽  
Noel Estrada-Merly ◽  
Ronald M. Sobecks ◽  
Betul Oran ◽  
...  

Abstract Background: Allogeneic hematopoietic cell transplantation (allo-HCT) remains the only curative therapeutic modality for patients with myelofibrosis (MF). However, the optimal conditioning regimen for allo-HCT either in the myeloablative conditioning (MAC) or in the reduced intensity conditioning (RIC) setting is not well known. Methods: Using the Center for International Blood and Marrow Transplant Research (CIBMTR) database, we identified adults aged ≥18 years with MF who underwent allo-HCT between the years 2008-2018. Donor types included matched sibling donor (MSD), 8/8 matched unrelated donor (MUD), and 7/8 MUD. Outcomes were compared separately in the MAC and RIC cohorts based on the most common conditioning regimens used in each setting - MAC [(Fludarabine/Busulfan (Flu/Bu) vs. Busulfan/cyclophosphamide (Bu/Cy)] or RIC [(Flu/Bu vs. Fludarabine/melphalan (Flu/Mel)]. Overall survival (OS), disease free survival (DFS), non-relapse mortality (NRM), relapse, acute and chronic graft versus host disease (GVHD) and GVHD-free relapse-free survival (GRFS) were evaluated. Survival analysis was done using Kaplan-Meier method and significant predictors were evaluated using Cox-proportional hazard regression method. Multivariable regression model included main effect (conditioning regimen) and covariates (patient age, gender, race, CMV match, disease subtype, DIPSS at HCT, comorbidities score (HCT-CI), Karnofsky performance status, prior therapy (ruxolitinib use/splenic radiation therapy/splenectomy), interval between diagnosis and transplant, conditioning intensity, stem cell source, donor-recipient HLA-match, GVHD prophylaxis, ATG/alemtuzumab use, transplant year, and center affect). All analyses were performed at a two-sided significance level of 0.05. Results: Of 872 patients who met the study criteria, 379 patients underwent allo-HCT using MAC (Flu/Bu=247, Bu/Cy=132) and 493 patients using RIC (Flu/Bu=166, Flu/Mel=327). Key baseline characteristics of the patients are summarized in Table 1. In multivariable analysis, significant differences in outcomes were observed in the MAC and RIC setting based on the choice of conditioning regimen (Table 2). In the MAC setting, Bu/Cy was associated with a higher risk of acute GVHD (grade 2-4 HR 2.33, 95% CI 1.67-3.25, p&lt;0.01; grade 3-4 HR 2.31, 95% CI 1.52-3.52, p&lt;0.01) and inferior GRFS (HR 1.94, 95% CI 1.49-2.53, p&lt;0.01) as compared to Flu/Bu. In the RIC setting, Flu/Mel was associated with inferior OS (HR 1.80, 95% CI 1.15-2.81, p&lt;0.01), higher risk of NRM (HR 1.81, 95% CI 1.12-2.91, p=0.01) and acute GVHD (grade 2-4- HR 1.45, 95% CI 1.03-2.03, p=0.03; grade 3-4 HR 2.21, 95%CI 1.28-3.83, p&lt;0.01) as compared to Flu/Bu. These higher risks associated with Flu/Mel were primarily observed early post-transplant. The results were consistent when the outcomes were evaluated based on the two common melphalan doses employed in the RIC setting (100mg/m 2 vs 140mg/m 2). Conclusions: Our study demonstrates that the choice of conditioning regimen significantly influences the outcomes of allo-HCT in MF. The results favor Flu/Bu based conditioning in the MAC (lesser acute GVHD and better GRFS) and RIC (better OS, lower NRM, lower acute GVHD) setting. Hence, this aspect should be explored in future studies as the modification of conditioning strategies could lead to improved outcomes. Figure 1 Figure 1. Disclosures Guru Murthy: TG therapeutics: Other: Advisory board; Cardinal Health Inc.: Honoraria; Qessential: Consultancy; Guidepoint: Consultancy; Techspert: Consultancy; Cancerexpertnow: Honoraria. Sobecks: CareDX: Membership on an entity's Board of Directors or advisory committees. Scott: Bristol Myers Squibb: Consultancy, Honoraria, Research Funding. Saber: Govt. COI: Other.


Blood ◽  
2016 ◽  
Vol 128 (22) ◽  
pp. 5809-5809
Author(s):  
YooJin Lee ◽  
Joon Seok Yoon ◽  
In Hee Lee ◽  
Joon Ho Moon ◽  
Sang Kyun Sohn

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.


2020 ◽  
Vol 4 (10) ◽  
pp. 2308-2316 ◽  
Author(s):  
Talha Badar ◽  
Aniko Szabo ◽  
Anjali Advani ◽  
Martha Wadleigh ◽  
Shukaib Arslan ◽  
...  

Abstract The availability and use of blinatumomab symbolizes a paradigm shift in the management of B-cell acute lymphoblastic leukemia (ALL). We conducted a retrospective multicenter cohort analysis of 239 ALL patients (227 relapsed refractory [RR], n = 227; minimal residual disease [MRD], n = 12) who received blinatumomab outside of clinical trials to evaluate safety and efficacy in the “real-world” setting. The median age of patients at blinatumomab initiation was 48 years (range, 18-85). Sixty-one (26%) patients had ≥3 prior therapies and 46 (19%) had allogeneic hematopoietic cell transplantation before blinatumomab. The response rate (complete remission/complete remission with incomplete count recovery) in patients with RR disease was 65% (47% MRD−). Among 12 patients who received blinatumomab for MRD, 9 (75%) patients achieved MRD negativity. In patients with RR disease, median relapse-free survival and overall survival (OS) after blinatumomab was 32 months and 12.7 months, respectively. Among patients who received blinatumomab for MRD, median relapse-free survival was not reached (54% MRD− at 2 years) and OS was 34.7 months. Grade ≥3 cytokine release syndrome, neurotoxicity, and hepatotoxicity were observed in 3%, 7%, and 10% of patients, respectively. Among patients who achieved complete remission/complete remission with incomplete count recovery, consolidation therapy with allogeneic hematopoietic cell transplantation retained favorable prognostic significance for OS (hazard ratio, 0.54; 95% confidence interval, 0.30-0.97; P = .04). In this largest “real-world” experience published to date, blinatumomab demonstrated responses comparable to those reported in clinical trials. The optimal sequencing of newer therapies in ALL requires further study.


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