scholarly journals Donor IFNL4 Genotype Is Associated with Transplant-Related Mortality after Unrelated Donor Myeloablative Hematopoietic Cell Transplantation in Patients with Acute Leukemia

Blood ◽  
2018 ◽  
Vol 132 (Supplement 1) ◽  
pp. 968-968
Author(s):  
Shahinaz M Gadalla ◽  
Tao Wang ◽  
Olusegun Onabajo ◽  
Youjin Wang ◽  
Michael D. Haagenson ◽  
...  
Keyword(s):  
Acute Leukemia ◽  
Cell Transplantation ◽  
Research Funding ◽  
Hematopoietic Cell Transplantation ◽  
Hematopoietic Cell ◽  
Taqman Assay ◽  
Unrelated Donor ◽  
Karnofsky Performance Score ◽  
Related Mortality

Abstract Introduction. Interferon Lambda 4 gene (IFNL4) encodes IFN-λ4 protein, a new member of the type-III interferon family. IFNL4 genotype (rs368234815-dG allele), defines the genetic ability to produce IFN-λ4 and has been associated with reduced clearance of hepatitis C virus (HCV) infection. Given antiviral activity and immune modulation properties of IFN-λ4, we hypothesized that IFNL4 genotype of recipient and/or donor may modulate post-transplant survival outcomes, possibly through control of viral infections, and/or alloreactivity. Methods. From the Center for International Blood and Marrow Transplant Research (CIBMTR) database, we randomly selected 627 patients who received unrelated hematopoietic cell transplantation (HCT) for acute myeloid leukemia (AML, N=449) or acute lymphocytic leukemia (ALL, N=178). The patients had to match the following criteria: 1) HCT between 2004 and 2012, 2) available pre-HCT blood sample for the donor and recipient, 3) 8/8 HLA matching, and 3) myeloablative conditioning. IFNL4 genotyping was completed for 619 donors and 522 recipients using a custom-designed TaqMan assay for rs368234815. Multivariable Cox proportional hazard models were used for statistical analyses. Follow-up ended in November 2017. Results. Median age at HCT was 40 years (range=<1-68). Most patients (66%, N=411) were in first complete remission, had a Karnofsky Performance Score (KPS) between 90-100% (70%, N=436), and received peripheral blood stem cell grafts (70%, N=439). The median post-HCT follow-up was 68 months (range=5-122). Donor IFNL4 genotype was associated with risk of transplant-related mortality (TRM); with 5 years probabilities=19%, 27%, and 30% for donor TT/TT (n=286), TT/dG (n=267), and dG/dG (n=64) genotypes, respectively, p=0.02. The results remained significant in multivariable analysis (p=0.002); compared with patients receiving HCT from donors with TT/TT genotype, with the HR=1.59 (95% CI=1.13-2.23, p=0.007) for TT/dG donors and HR=1.95 (95% CI=1.18-3.23, p=0.009) for dG/dG donors. The data suggested that donor IFNL4 genotype may also predict risk of disease-free survival (DFS; HR=1.43, 95% CI=1.02-2.00, p=0.03), and overall survival (OS; HR=1.40 (95% CI=0.98-1.99, p=0.06) for donor dG/dG genotype (Table1). No association between recipient genotype and any survival outcome was observed (p>0.05 for OS, DFS, and TRM) Conclusions. Donor IFNL4 genotype is associated with risk of transplant-related mortality in patients with acute leukemia. The data suggest that avoiding donors with dG/dG genotype will improve HCT outcomes without limiting the potential donor pool. A validation study is needed; if confirmed, IFNL4 genotype may provide an added value to donor selection criteria. Disclosures Lee: Onyx: Research Funding; Kadmon: Research Funding; Amgen: Consultancy, Research Funding; Mallinckrodt: Honoraria; Incyte: Consultancy; Pfizer: Consultancy; Takeda: Research Funding.

Management of Anticoagulation in Patients with Hematologic Malignancy Undergoing Autologous Hematopoietic Cell Transplantation

Blood ◽  
2016 ◽  
Vol 128 (22) ◽  
pp. 1437-1437
Author(s):  
Ang Li ◽  
Chris Davis ◽  
Qian Wu ◽  
Madeline F Kesten ◽  
Ajay K Gopal ◽  
...  
Keyword(s):  
Cell Transplantation ◽  
Major Bleeding ◽  
Research Funding ◽  
Platelet Transfusion ◽  
Hematopoietic Cell Transplantation ◽  
Hematologic Malignancy ◽  
Hematopoietic Cell ◽  
Transfusion Threshold ◽  
Autologous Hct

Abstract Introduction: Venous thromboembolism (VTE) is a significant cause of morbidity in patients with hematologic malignancy who undergo hematopoietic cell transplantation (HCT); however, clinically significant bleeding is not uncommon in this setting and anticoagulation is often contraindicated during prolonged periods of severe thrombocytopenia. This study aims to determine the relative risks of continuing versus temporarily withholding therapeutic anticoagulation during periods of chemotherapy-induced thrombocytopenia in patients who undergo autologous HCT. Methods: Adult patients with hematologic malignancies who underwent first autologous HCT at our institution between 2006 and 2015 were selected. Among those, patients with VTE (as identified by ICD9 code and confirmed by chart review) that occurred in the year preceding transplant were selected as the study population. Patients were allocated into two cohorts at the onset of thrombocytopenia based on whether they continued anticoagulation using a high platelet transfusion threshold (50k), or whether they temporarily withheld anticoagulation using a standard platelet transfusion threshold (10k) and restarted treatment upon platelet engraftment. Patient characteristics and VTE risk factors were captured, depicted as number (percentage) and median (interquartile range), and compared using Fisher's exact and rank sum tests. Primary outcomes included rate of VTE extension/recurrence (assessed by appropriate imaging modality) and major bleeding (defined as grade 3 or 4 bleeding by WHO criteria) by 30 days. Secondary outcomes included clinical bleeding (grade 2-4), overall mortality, median number of platelet and red blood cell (RBC) transfusion, median time to neutrophil and platelet engraftment. Pre-defined exploratory subgroup analysis was performed. Logistic regression, Cox regression, and linear regression models without adjustment were generated for outcomes where a P value of < 0.05 was considered significant (Stata 14.1). Results: Among 1,631 patients who underwent first autologous HCT between 2006 and 2015, 204 patients developed VTE (12.5%) in the year preceding transplant. The median duration of thrombocytopenia, defined as the period during which the platelet < 50k, was 12 days. The median follow-up period was 359 days and only 4% of patients were lost to follow up prior to 30 days. In addition to routine clinical assessment for VTE and bleeding, repeat imaging surveillance was done in 55% of patients prior to discharge from the transplant service. Except for the timing of prior VTE occurrence, there were no significant differences in baseline characteristics between the cohort that continued anticoagulation (N=132) and the cohort that discontinued anticoagulation (N=72) (Table 1). There were no significant differences in the rate of VTE extension/recurrence or major bleeding between the treatment groups by 30 days (Table 2). The rates of VTE in both groups were low (1 new pulmonary embolism and 2 new catheter-associated thromboses). There was 1 fatal spontaneous retroperitoneal bleeding (grade 4) in the cohort that continued anticoagulation. The number of platelet transfusions was significantly higher in the patients who continued anticoagulation. Further comparison of the 2 cohorts by different subgroups did not reveal significant interactions (Figure 1, all interaction P values > 0.300). Conclusions: In patients undergoing HCT for hematologic malignancy who also have VTE, continuation of anticoagulation (compared to temporary cessation) during chemotherapy-induced thrombocytopenia is associated with increased platelet utilization but no significant difference in the rate of VTE extension/recurrence. The low rate of recurrent thrombosis among patients who discontinued anticoagulation during pre-engraftment thrombocytopenia suggests that temporary interruption of anticoagulation may be the better option for selected patients who face this difficult clinical situation. Disclosures Gopal: Seattle Genetics: Research Funding. Garcia:Daiichi Sankyo: Consultancy, Research Funding; Pfizer: Consultancy; Boehringer Ingelheim: Consultancy; BMS: Consultancy; Janssen: Consultancy, Research Funding.

scholarly journals Validation of Different Prognostic Scores in Allogeneic Hematopoietic Cell Transplantation in the Post-Transplant Cyclophosphamide Era

Blood ◽  
2021 ◽  
Vol 138 (Supplement 1) ◽  
pp. 3925-3925
Author(s):  
Maria Queralt Salas ◽  
Luis Gerardo Rodríguez-Lobato ◽  
María Suárez-Lledó ◽  
Nuria Martínez-Cibrian ◽  
Teresa Solano ◽  
...  
Keyword(s):  
Cell Transplantation ◽  
Research Funding ◽  
Operating Characteristic ◽  
Hematopoietic Cell Transplantation ◽  
Hematopoietic Cell ◽  
Prognostic Scores ◽  
Predictive Capacity ◽  
Post Transplant ◽  
Gvhd Prophylaxis

Abstract INTRODUCTION The use of post-transplantation cyclophosphamide (PTCy) for graft-versus-host disease (GvHD) prophylaxis has decreased the rates of this complication, resulting on an improvement of transplant-related toxicity and survival. Secondary to its efficacy, the use of PTCy has been almost universally integrated for allogeneic hematopoietic cell transplantation (alloHCT), independently of the selected donor source. Clinical decisions in alloHCT are supported by the use of prognostic scores for outcome prediction. However, capability of prediction by diverse scores can vary depending on their features and on the composition of the study cohort. Additionally, the continuous innovation on alloHCT techniques and practices leads to an ongoing need to update risk indices aimed at improving risk stratification of patients undergoing alloHCT. This study explores the predictive capacity of different prognostic scores routinely used in alloHCT, in a contemporaneous cohort of adults undergoing peripheral blood (PB) alloHCT using PTCy-based GvHD prophylaxis. METHODS Between 2014 and 2020, 230 consecutive adults with hematological malignancies underwent PB-alloHCT with PTCy-based GvHD prophylaxis at our Institution. Data related to Hematopoietic Cell Transplantation-Comorbidity Index (HCT-CI), Karnosfky Performance Status (KPS), Disease Risk Index (DRI), European Bone Marrow Transplantation (EBMT) score, and Endothelial Activation and Stress Index (EASIX) were collected retrospectively. Complete information was available for 216 patients. Overall survival (OS) was considered the main outcome variable. Patients were grouped into two risk groups based on the optimal cut-off value for each score. In the case of EASIX, 1.578 was the most discriminating cut-off for OS. The score discrimination for OS was measured independently for each index using the receiver operating characteristic curve (AUC) calculated using receiver operating characteristic (ROC) curves, and determined at different time-points after alloHCT. RESULTS Of the 216 patients included, the median age was 52 years (range: 18-70), acute myeloid leukemia (36.1%) was the most prevalent baseline diagnosis, 42.1% of adults underwent reduced-intensity conditioning alloHCT, 69.4% received grafts from unrelated donors, and 23.0% from haploidentical donors. With a median follow-up of 22.6 months, 24.1% patients relapsed, and 2-y OS and non-relapse mortality were 67.3% and 19.9%. DRI, HCT-CI, KPS, and EASIX successfully grouped patients into higher and lower risk strata, supporting their use for risk classification. HCT-CI [(score&gt;3 (vs 0-3): HR 2.02, p&lt;0.01], DRI [High - Very High risk (vs Low - Int): HR 2.08, p&lt;0.01], and EASIX [&gt;1.578 (vs ≤ 1.578): HR 1.73, p&lt;0.02], maintained an optimal discrimination capacity during the entire post-transplant follow-up (median AUC ranges &gt; 55%). DRI was the most accurate prognostic index during the entire post-transplant period (median AUC ranges &gt; 60%). KPS score was found to be a useful predictor of mortality up to the first year after alloHCT and with the highest prognostic accuracy at 3 months (AUC 67.09%). HCT-CI score was found to present a better discrimination capacity once elapsed 6 months after alloHCT and with a peak of prediction capacity at 2 years (AUC 60.3%). EASIX, when measured at the pre-transplant evaluation, demonstrated to have acceptable predictive ability during the entire post-transplant period (median AUC &gt; 55%), and with a peak of prediction at 3 months (AUC 62.6%). The EBMT score had the lowest predictive capacity in our analysis (Figure 1). CONCLUSION: This study validates, for the first time, the risk stratification capacity for OS of DRI, HCT-CI, KPS, and EASIX in PB-alloHCT with PCTy-based prophylaxis. Interestingly, the prediction accuracy of the prognostic scores differed depending on the time-period. This result can be taken into consideration to enhance the applicability of these scores and refine the clinical decisions taken based on the information provided from their use in routine clinical practice. Figure 1 Figure 1. Disclosures Lozano: Terumo BCT: Honoraria, Research Funding; Macopharma: Research Funding; Grifols: Honoraria. Rosinol: Janssen, Celgene, Amgen and Takeda: Honoraria. Esteve: Novartis: Consultancy, Research Funding; Astellas: Consultancy; Jazz: Consultancy; Pfizer: Consultancy; Novartis: Research Funding; Abbvie: Consultancy; Bristol Myers Squibb/Celgene: Consultancy.

scholarly journals How I treat measurable (minimal) residual disease in acute leukemia after allogeneic hematopoietic cell transplantation

Blood ◽  
2020 ◽  
Vol 135 (19) ◽  
pp. 1639-1649 ◽  
Author(s):  
Alexandros Spyridonidis
Keyword(s):  
Acute Leukemia ◽  
Minimal Residual Disease ◽  
Cell Transplantation ◽  
Hematopoietic Cell Transplantation ◽  
Residual Disease ◽  
Hematopoietic Cell ◽  
Allogeneic Hematopoietic Cell Transplantation ◽  
Leukemia Relapse ◽  
Minimal Residual

Abstract Although allogeneic hematopoietic cell transplantation (allo-HCT) is currently the standard curative treatment of acute leukemia, relapse remains unacceptably high. Measurable (minimal) residual disease (MRD) after allo-HCT may be used as a predictor of impending relapse and should be part of routine follow-up for transplanted patients. Patients with MRD may respond to therapies aiming to unleash or enhance the graft-versus-leukemia effect. However, evidence-based recommendations on how to best implement MRD testing and MRD-directed therapy after allo-HCT are lacking. Here, I describe our institutional approach to MRD monitoring for preemptive MRD-triggered intervention, using patient scenarios to illustrate the discussion.

The outcome of two or more HLA loci mismatched unrelated donor hematopoietic cell transplantation for acute leukemia: an ALWP of the EBMT study

2020 ◽  
Vol 56 (1) ◽  
pp. 20-29
Author(s):  
Arnon Nagler ◽  
Bhagirathbhai Dholaria ◽  
Myriam Labopin ◽  
Benedetto Bruno ◽  
Alessandro Rambaldi ◽  
...  
Keyword(s):  
Acute Leukemia ◽  
Cell Transplantation ◽  
Hematopoietic Cell Transplantation ◽  
Hematopoietic Cell ◽  
Unrelated Donor

scholarly journals Higher Efficacy of TBI + Cyclophosphamide Than TBI + Fludarabine As Conditioning Prior to Allogeneic Hematopoietic Cell Transplantation for Acute Lymphoblastic Leukemia: An Analysis By the Acute Leukemia Working Party of the EBMT

Blood ◽  
2021 ◽  
Vol 138 (Supplement 1) ◽  
pp. 2876-2876
Author(s):  
Sebastian Giebel ◽  
Myriam Labopin ◽  
Gerard Socie ◽  
Mahmoud Aljurf ◽  
Urpu Salmenniemi ◽  
...  
Keyword(s):  
Stem Cells ◽  
Acute Lymphoblastic Leukemia ◽  
Cell Transplantation ◽  
Research Funding ◽  
Hematopoietic Cell Transplantation ◽  
Lymphoblastic Leukemia ◽  
Hematopoietic Cell ◽  
Allogeneic Hematopoietic Cell Transplantation ◽  
Karnofsky Performance Score ◽  
Increased Risk

Abstract BACKGROUND: Allogeneic hematopoietic cell transplantation (allo-HCT) is a standard of care for adults with high-risk acute lymphoblastic leukemia (ALL) in first or subsequent complete remission (CR). Myeloablative total body irradiation (TBI) combined with cyclophosphamide (Cy) is the most frequently used conditioning regimen. In order to reduce toxicity Cy may be replaced by fludarabine (Flu). The goal of this registry-based, retrospective study was to compare outcomes of allo-HCT following TBI/Cy vs. TBI/Flu conditioning. PATIENTS AND METHODS: Included in the analysis were 2255 patients aged 18-65 years, treated with allo-HCT from either a matched sibling (43%) or unrelated (57%) donor in CR1 (83%) or CR2 (17%), between the years 2010-2020. Patients with Ph(-) B-ALL, Ph(+) B-ALL, and T-ALL were represented in equal proportions. TBI 12Gy + Cy was used in 2105 cases while TBI 12Gy + Flu was administered to 150 patients. Patients treated with TBI/Flu were significantly older (median 35 years vs. 33 years, p=0.006), with poorer Karnofsky performance score (&lt;90, 27% vs. 20%, p=0.03), more frequently transplanted from unrelated donors (71% vs. 57%, p=0.0007) with less frequently use of bone marrow as a source of stem cells (5% vs. 21%, p&lt;0.0001), and in more recent year (median 2018 vs. 2015, p&lt;0.0001). RESULTS: Engraftment rate was 99% for both TBI/Cy and TBI/Flu patients. In a univariate analysis the use of TBI/Cy as compared to TBI/Flu was associated with a tendency to reduced incidence of relapse (24% vs. 29% at 2 years, p=0.1), increased incidence of grade 2-4 acute graft versus host disease (GVHD, 35.5% vs. 28%, p=0.08) and improved leukemia-free survival (LFS, 62% vs. 57%, p=0.18). The rates and causes of non-relapse mortality (NRM) did not differ significantly between the two conditioning groups. In a multivariate model adjusted for other prognostic factors, TBI/Cy conditioning was associated with reduced risk of relapse (HR=0.69, p=0.049) and increased risk of grade 2-4 acute GVHD (HR=1.57, p=0.03) without significant effect on other transplantation outcomes. An additional analysis was performed with TBI/Cy treated patients (n=132) matched strictly to those treated with TBI/Flu (n=132) in terms of disease subtype, disease status and donor type with the nearest neighbor for patient age, patient and donor sex, in vivo T-cell depletion, Karnofsky score and source of stem cells; the use of TBI/Cy as compared to TBI/Flu was associated with significantly reduced rate of relapse (18% vs. 30% at 2 years, p=0.015) and a tendency to an improved LFS (65% vs. 59%, p=0.07) and overall survival (OS, 73% vs. 68%, p=0.16) without effect on NRM and GVHD. CONCLUSIONS: The use of myeloablative TBI/CY as conditioning prior to allo-HCT for adult patients with ALL in CR1 or CR2 is associated with stronger anti-leukemic effect leading to significantly lower relapse rate compared to TBI/Flu and therefore should be likely considered a preferable regimen. Disclosures Giebel: Janssen: Honoraria, Speakers Bureau; Pfizer: Consultancy, Honoraria, Speakers Bureau; Novartis: Consultancy, Honoraria, Speakers Bureau; Amgen: Consultancy, Honoraria, Speakers Bureau. Labopin: Jazz Pharmaceuticals: Honoraria. Socie: Alexion: Research Funding. Yakoub-Agha: Jazz Pharmaceuticals: Honoraria. Kröger: Novartis: Research Funding; Riemser: Honoraria, Research Funding; Sanofi: Honoraria; Neovii: Honoraria, Research Funding; Jazz: Honoraria, Research Funding; Gilead/Kite: Honoraria; Celgene: Honoraria, Research Funding; AOP Pharma: Honoraria. Forcade: Novartis: Consultancy, Other: Travel Support, Speakers Bureau; Gilead: Other: Travel Support, Speakers Bureau; Jazz: Other: Travel Support, Speakers Bureau; MSD: Other: Travel Support. Huynh: Jazz Pharmaceuticals: Honoraria. Spyridonidis: Menarini: Current Employment. Perić: therakos: Honoraria; servier: Honoraria; MSD: Honoraria; Astellas: Honoraria; NOVARTIS: Honoraria; Abbvie: Honoraria; Pfizer: Honoraria. Mohty: Pfizer: Honoraria; Celgene: Honoraria, Research Funding; Amgen: Honoraria; Astellas: Honoraria; Gilead: Honoraria; Jazz: Honoraria, Research Funding; Janssen: Honoraria, Research Funding; Novartis: Honoraria; Bristol Myers Squibb: Honoraria; Takeda: Honoraria; Sanofi: Honoraria, Research Funding; Adaptive Biotechnologies: Honoraria.

Comparable Survival and Transplant-Related Mortality Following Allogeneic Hematopoietic Cell Transplantation from HLA Allele-Matched Unrelated and HLA-Identical Sibling Donors.

Blood ◽  
2006 ◽  
Vol 108 (11) ◽  
pp. 3146-3146 ◽  
Author(s):  
Thai M. Cao ◽  
Schickwann Tsai ◽  
Linda Kelley ◽  
Stephen C. Alder ◽  
Thomas C. Fuller ◽  
...  
Keyword(s):  
Overall Survival ◽  
Cell Transplantation ◽  
Acute Gvhd ◽  
Hematopoietic Cell Transplantation ◽  
Chronic Gvhd ◽  
Hematopoietic Cell ◽  
Allogeneic Hematopoietic Cell Transplantation ◽  
P Value ◽  
Unrelated Donor ◽  
Related Mortality

Abstract Comprehensive analyses of unrelated donor (URD) and recipient HLA-matching for allogeneic hematopoietic cell transplantation (AHCT) have demonstrated better outcomes when allele typing is performed using high-resolution nucleotide sequence-based techniques. To evaluate survival following myeloablative AHCT using allele-level HLA-matched URD as compared with HLA-identical sibling donors, we analyzed outcomes for 430 patients treated at our center between March 1991 and April 2005. Sequence-based allele typing was retrospectively performed for HLA-A, B, C, DR and DQ when not done at time of AHCT for URD (n = 124; 29%) and non-sibling related donors (n = 19; 4%). Donors were HLA-identical siblings (n = 276; 64%), HLA allele-matched URD (n = 52; 12%), single HLA-locus mismatched donors (n = 52; 12%), or > 1 locus mismatched donors (n = 50; 12%). The median age at transplant was 23.4 years (range: 0.2 – 61). The most common diagnoses were AML (n = 107; 25%), CML (n = 90; 21%), ALL (n = 86; 20%) and MDS (n = 50; 12%). Total body irradiation-based preparative regimens were used for 283 patients (66%). Bone marrow (BM) was the graft for 388 patients (90%) and GCSF-mobilized peripheral blood stem cells (PBSC) for the remaining 42 (10%). Graft-versus-host disease (GVHD) prophylaxes were cyclosporine and methotrexate (n = 327; 76%), long methotrexate (n = 42; 10%), T-cell depletion (n = 19; 4%), or other regimens (n = 42; 10%). With a median follow-up of 4.8 years (range: 0.2 – 12.1), the 5-year estimate of overall survival (OS) for the entire group was 48.2% (95% CI: 45.7 – 50.7) and transplant-related mortality (TRM) was 31.4% (95% CI: 28.8 – 34). As shown in the Table, OS and TRM were indistinguishable between AHCT performed with HLA-identical siblings compared with HLA allele-matched URD. There was also no difference in grade III – IV acute GVHD (P = .46) between these two groups whereas there was a trend towards more extensive chronic GVHD (HR 1.8; 95% CI: 0.9 – 3.6; P = 0.12) for the URD recipients. Using a multivariate analysis to adjust for advanced disease, age (> vs ≤ 30 years), graft (BM vs PBSC) and female-to-male gender mismatch, there remained no difference in OS between HLA-identical siblings and HLA allele-matched URD (P = 0.67). These results demonstrate that key outcomes (OS, TRM, and severe acute GVHD) are equivalent in recipients of grafts from either allele-level 10/10 HLA-matched URD or HLA-identical siblings. Overall Survival TRM Number Hazard Ratio 95% CI P value Hazard Ratio95% CI P value HLA-ID Sibling 276 1 - - 1 - - HLA-ID URD 52 1.1 0.7 – 1.7 0.67 0.8 0.4 – 1.6 0.58 1 Locus MM 52 1.3 0.9 – 2.0 0.19 1.4 0.8 – 2.4 0.25 > 1 Locus MM 50 2.0 1.4 – 2.9 < 0.001 2.6 1.7 – 4.1 < 0.001

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 Early transplantation-related mortality after allogeneic hematopoietic cell transplantation in patients with acute leukemia

BMC Cancer ◽  
2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Seom Gim Kong ◽  
Seri Jeong ◽  
Sangjin Lee ◽  
Jee-Yeong Jeong ◽  
Da Jung Kim ◽  
...  
Keyword(s):  
Acute Leukemia ◽  
Cell Transplantation ◽  
Hematopoietic Cell Transplantation ◽  
Cord Blood Transplantation ◽  
Iron Chelation ◽  
Incidence Rates ◽  
Hematopoietic Cell ◽  
Allogeneic Hematopoietic Cell Transplantation ◽  
Blood Transplantation ◽  
Related Mortality

Abstract Background Transplantation-related mortality (TRM) is a major obstacle in allogeneic hematopoietic cell transplantation (allo-HCT). Approximately 60–80% of TRM occurs early, within 100 days of transplantation. Methods This was a nationwide population cohort study involving 5395 patients with acute leukemia who underwent allo-HCT between 2003 and 2015. Patient data were collected from the Korean National Health Insurance Service database. We investigated the cumulative incidence rates (CIRs) of early TRM at 50 and 100 days. Results The CIRs of early TRM at 50 and 100 days were 2.9 and 8.3%, respectively. There was no decrease in the CIRs of early TRM over time. The early mortality was significantly higher in patients with more than 9 months between the diagnosis and transplantation (CIRs of TRM at 50, 100 days; 6.0, 13.2%), previous transplantations (CIRs of TRM at 50, 100 days; 9.4, 17.2%), and cord blood transplantation (CIRs of TRM at 50, 100 days; 6.1, 8.3%). The early TRM was significantly lower in patients who received iron chelation before transplantation (CIRs of TRM at 50, 100 days; 0.3, 1.8%). Conclusions In conclusion, the overall CIR of early TRM was less than 10%. The predictable factors for early TRM included age, time from diagnosis to transplantation, the number of prior transplantations, the graft source, and previous iron chelation therapy.

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