scholarly journals HLA-Mismatch Is Associated with Worse Outcomes after Myeloablative Conditioning and Unrelated Donor Hematopoietic Cell Transplantation: A Cibmtr Analysis

2014 ◽  
Vol 20 (2) ◽  
pp. S25-S26 ◽  
Author(s):  
Joseph Pidala ◽  
Stephanie J. Lee ◽  
Stephen R. Spellman ◽  
Hailin Wang ◽  
Kwang Woo Ahn ◽  
...  
Keyword(s):  
Cell Transplantation ◽  
Hematopoietic Cell Transplantation ◽  
Hematopoietic Cell ◽  
Unrelated Donor ◽  
Myeloablative Conditioning

scholarly journals Clinical Relevance of HLA Supertype Matching after Myeloablative Conditioning 7/8 Unrelated Donor Hematopoietic Cell Transplantation: A CIBMTR Study

Blood ◽  
2014 ◽  
Vol 124 (21) ◽  
pp. 2572-2572
Author(s):  
Aleksandr Lazaryan ◽  
Tao Wang ◽  
Stephen R. Spellman ◽  
Hai-Lin Wang ◽  
Carlheinz R. Müller ◽  
...  
Keyword(s):  
Clinical Outcomes ◽  
Cell Transplantation ◽  
Hematopoietic Cell Transplantation ◽  
Hla Class I ◽  
Hematopoietic Cell ◽  
Class I ◽  
Unrelated Donor ◽  
Myeloablative Conditioning ◽  
Increased Risk ◽  
The Impact

Abstract The diversity of the HLA class I and II alleles can be simplified by consolidating them into fewer supertype clusters based on functional or predicted structural similarities in epitope binding grooves of HLA molecules. HLA class I and II supertypes have been increasingly studied in association with immune susceptibility to infection and cancer with potential implications for vaccine development. However, the significance of individual allele mismatching within and outside of HLA class I or II supertypes remains unknown in the context of hematopoietic cell transplantation (HCT). We therefore studied the impact of HLA supertype disparities on clinical outcomes of 1934 patients with AML (45%), ALL (31%), CML (14%) or MDS (9%) who underwent 7/8 unrelated donor myeloablative conditioning HCT from 1999 to 2011 and were registered with CIBMTR. Median age at transplant was 35 years (range, 1-70); 53% were males; 81% Caucasian; 56% received peripheral blood grafts; 50% were ABO-mismatched; 36% had in-vivo T-cell depletion; 62% received tacrolimus- and 36% cyclosporine A-based GVHD prophylaxis; 72% male or non-parous female donors; median follow up of survivors was 54 months (3-149). Supertype assignment methods of (1) revised main HLA anchor specificities (Sydney, 2008) and (2) bioinformatics (Doytchinova, 2004-05) were used to categorize single mismatched alleles into 6 HLA-A (A01, A01A03, A01A24, A02, A03, A24), 6 HLA-B (B07, B08, B27, B44, B58, B62), 2 HLA-C (C1, C2), and 5 DRB1 (DR1, DR3, DR4, DR5, DR9) supertypes. Overall survival (OS), disease-free survival (DFS), relapse, treatment-related mortality (TRM), acute graft vs. host disease (aGVHD) and chronic GVHD were compared across matched vs. mismatched HLA-A (265 vs. 429), -B (230 vs. 92), -C (365 vs. 349), and -DRB1 (153 vs. 51) supertypes. We used predetermined α=0.01 for statistical significance as multiple exploratory analyses were conducted by Kaplan-Meier, Gray, and Cox proportional hazard methods. In the multivariable analysis, supertype B-mismatch was associated with increased risk of grade II-IV aGVHD (HR=1.78; 95% CI, 1.23-2.59, p=0.0025), however no difference was found for grade III-IV aGVHD or other clinical outcomes compared to supertype B-matches. Supertype DRB1-mismatch was associated with shorter neutrophil recovery (HR=0.51; 95% CI, 0.36-0.71, p=0.0001), yet a trend toward inferior OS (HR=1.58; 95% CI 1.04-2.38, p=0.037) and higher TRM (HR=1.64; 95% CI, 0.99-2.74, p=0.0565) compared to DRB1 matches within supertypes. There was no increased risk of GVHD with DRB1 supertype mismatch. No associations were observed between HLA-A and -C supertypes or aggregate supertype-matched vs. -mismatched groups for any outcomes. Our analysis demonstrated differential influence of HLA supertype-based allele matching within -B and -DRB1 loci on clinical outcomes after myeloablative 7/8 URD HCT. Disclosures No relevant conflicts of interest to declare.

scholarly journals Comparative Effectiveness of Busulfan/Cyclophosphamide Versus Busulfan/Fludarabine Myeloablative Conditioning for Allogeneic Hematopoietic Cell Transplantation in Acute Myeloid Leukemia

Blood ◽  
2018 ◽  
Vol 132 (Supplement 1) ◽  
pp. 3365-3365
Author(s):  
Sagar S. Patel ◽  
Lisa Rybicki ◽  
Arden Emrick ◽  
Victoria Winslow ◽  
Jamie Starn ◽  
...  
Keyword(s):  
Acute Myeloid Leukemia ◽  
Cell Transplantation ◽  
Myeloid Leukemia ◽  
Somatic Mutations ◽  
Hematopoietic Cell Transplantation ◽  
Hematopoietic Cell ◽  
Unrelated Donor ◽  
Myeloablative Conditioning ◽  
Post Transplant ◽  
Acute Myeloid

Abstract Background Myeloablative conditioning (MAC) is a standard approach for allogeneic hematopoietic cell transplantation (alloHCT), but is associated with risks of morbidity and mortality. As regimen intensity affects post-transplant outcomes, assessment of pre-transplant cytogenetics and somatic mutations may refine which acute myeloid leukemia (AML) patients benefit the most. We compared the effectiveness of two approaches: busulfan/cyclophosphamide (Bu/Cy) and the MAC, but reduced toxicity regimen busulfan/fludarabine (Bu/Flu). Moreover, it is unclear whether somatic mutations in AML may differentially affect post-transplant outcomes between these regimens. We hypothesized that despite relative differences with these regimens, they may result in comparable outcomes. Methods We conducted a single center, retrospective analysis of adult AML patients in CR1 or CR2 who underwent a first T-cell replete HLA-8/8 matched related or unrelated donor alloHCT. Patients received either parenteral Bu (12.8 mg/kg total over 4 days) with Cy (120 mg/kg total over 2 days) or parenteral Bu (400 mg/m2 total over 4 days) with Flu (160 mg/m2 total over 4 days). Bu dose adjustment was not used in either cohort. In addition to cytogenetic risk group stratification by European LeukemiaNet criteria (Döhner H, et al, Blood 2016), a subset of patients had a 36-gene somatic mutation panel assessed prior to alloHCT by next-generation sequencing. Pre-transplant characteristics were compared between regimens with Chi-square, Fisher's exact, or Wilcoxon rank sum tests. Differing characteristics were included in a multivariable Fine and Gray regression model with results as hazard ratios (HR) and 95% confidence intervals (CI). Results From 2008 - 2017, 76 AML patients receiving Bu/Cy and 50 receiving Bu/Flu were identified meeting inclusion criteria (Bu/Flu used starting in 2010). Median age at transplant was 51 (21-61) years for Bu/Cy vs. 64 (34-74) for Bu/Flu (P<0.001). The cohorts were otherwise comparable in regards to gender, race, performance status, HCT-CI, and disease status at alloHCT. Bu/Cy vs. Bu/Flu patients had 16% vs. 10% favorable, 66% vs. 50% intermediate, and 18% vs. 40% adverse-risk cytogenetics (P=0.033). The most common somatic mutations in the Bu/Cy cohort were FLT3 (20%), NPM1 (18%), DNMT3A (16%), TET2 (9%), CEBPA (5%), and IDH1 (5%). In the Bu/Flu cohort, these were FLT3 (20%), NPM1 (18%), NRAS (12%), TET2 (12%), and DNMT3A (10%). There were no significant differences in somatic mutations between the cohorts, except for a higher incidence of NRAS in the Bu/Flu cohort (12% vs. 4%, P=0.029). Bu/Flu patients were more likely to have an unrelated donor (70% vs. 47%, P=0.012) and receive a peripheral blood stem cell (PBSC) graft (94% vs. 17%, P<0.001). As such, Bu/Flu patients had more rapid neutrophil (median 13 vs. 14 days, P=0.009) and platelet (median 15 vs. 20 days, P<0.001) recovery and a shorter length of hospital stay (LOS) (median 22 vs. 27 days, P<0.001). In multivariable analysis, Bu/Flu patients trended towards more chronic graft-versus-host-disease (GvHD; any stage) (HR 0.42, CI 0.16-1.11, P=0.08), but there were no other differences in CMV infections, other infections, acute GvHD, relapse, relapse mortality (RM), non-relapse mortality (NRM), relapse-free (RFS), and overall survival (OS). 58% of Bu/Cy and 56% of Bu/Flu patients remain alive with median follow-up of 59 and 22 months, respectively (P=0.003). The most common causes of death for these respective cohorts were relapse (50% vs. 41%) and infection (16% vs. 27%). Conclusion Bu/Cy and Bu/Flu in alloHCT for AML results in comparable incidences of infection, GvHD, RM, NRM, RFS, and OS. This was despite Bu/Flu patients being older and more likely to have adverse cytogenetics and an unrelated donor. Bu/Flu is better tolerated with less toxicity. Faster hematopoietic recovery and shorter LOS with Bu/Flu reflects PBSC graft use and has implications for health care resource utilization. Future prospective studies with larger cohorts and cost-effectiveness analyses comparing these conditioning strategies are warranted. In this analysis, no mutations appeared to be sensitive to use of the more intensive regimen, Bu/Cy. Further investigation of pre-transplant or post-transplant persistence of somatic mutations may risk stratify those who may benefit from more intensive or innovative approaches to prevent relapse after transplant. Disclosures Gerds: Apexx Oncology: Consultancy; Celgene: Consultancy; CTI Biopharma: Consultancy; Incyte: Consultancy. Majhail:Incyte: Honoraria; Atara: Honoraria; Anthem, Inc.: Consultancy.

Comparing morbidity and mortality of HLA-matched unrelated donor hematopoietic cell transplantation after nonmyeloablative and myeloablative conditioning: influence of pretransplantation comorbidities

Blood ◽  
2004 ◽  
Vol 104 (4) ◽  
pp. 961-968 ◽  
Author(s):  
Mohamed L. Sorror ◽  
Michael B. Maris ◽  
Barry Storer ◽  
Brenda M. Sandmaier ◽  
Razvan Diaconescu ◽  
...  
Keyword(s):  
Cell Transplantation ◽  
Hematopoietic Cell Transplantation ◽  
Hazard Ratio ◽  
Hematopoietic Cell ◽  
Morbidity And Mortality ◽  
Unrelated Donor ◽  
Matched Unrelated Donor ◽  
Myeloablative Conditioning ◽  
Comorbidity Scores ◽  
Patient Groups

AbstractWe have carried out HLA-matched unrelated donor hematopoietic cell transplantation (HCT) after nonmyeloablative conditioning in patients with hematologic malignancies who were ineligible for conventional transplantations because of age, comorbidities, or both. The nonmyeloablative regimen consisted of 90 mg/m2 fludarabine and 2 Gy total body irradiation given before and mycophenolate mofetil and cyclosporine given after HCT. This report compares, retrospectively, morbidity and mortality among 60 consecutive patients given nonmyeloablative conditioning (nonablative patients) to those among 74 concurrent and consecutive patients given myeloablative conditioning (ablative patients) before unrelated HCT. The Charlson Comorbidity Index was used to assess pretransplantation comorbidities. Even though nonablative patients had significantly higher pretransplantation comorbidity scores, were older, and had more often failed preceding ablative transplantations and cytotoxic therapies, they experienced fewer grades III to IV toxicities than ablative patients. Further, the incidence of grades III to IV acute graft-versus-host disease (GVHD) was significantly lower in nonablative patients. Both patient groups had comparable 1-year probabilities of chronic GVHD. The 1-year nonrelapse mortality rate was 20% in nonablative patients compared to 32% in ablative patients (hazard ratio = 1.4). After adjustment for pretransplantation differences between the 2 patient groups, the hazard ratio was 3.0 (P = .04). Multivariate analyses showed higher pretransplantation comorbidity scores to result in increased toxicity and mortality.

Efficacy of keratinocyte growth factor in prevention of oral mucositis in children undergoing allogeneic hematopoietic cell transplantation

2020 ◽  
Vol 51 (3) ◽  
pp. 172-178
Author(s):  
Natalia Bartoszewicz ◽  
Krzysztof Czyżewski ◽  
Robert Dębski ◽  
Anna Krenska ◽  
Ewa Demidowicz ◽  
...  
Keyword(s):  
Growth Factor ◽  
Cell Transplantation ◽  
Oral Mucositis ◽  
Hematopoietic Cell Transplantation ◽  
Clinical Course ◽  
Keratinocyte Growth Factor ◽  
Supportive Therapy ◽  
Primary Objective ◽  
Hematopoietic Cell ◽  
Unrelated Donor

AbstractIntroductionOral mucositis is regarded by patients as one of the worst and debilitating complications of conditioning and hematopoietic cell transplantation (HCT). Prevention of mucositis is one of the priorities of supportive therapy during and after conditioning.ObjectivesThe primary objective of the study was the analysis of efficacy of keratinocyte growth factor (KGF, palifermin) used in prophylaxis of oral mucositis in patients undergoing allo-HCT. The secondary objectives of the study included the analysis of the influence of palifermin on clinical course of oral mucositis and early transplant outcomes, as well as analysis of the contraindications of palifermin in patients undergoing allo-HCT.Patients and methodsA total number of 253 allo-HCT performed between 2003 and 2018 in patients aged 0–19 years in a single center were analyzed. Overall, in 161 HCTs, palifermin was administered.ResultsPatients receiving KGF were transplanted earlier in the context of calendar year, and more often received ATG, mainly due to the higher rate of unrelated donor transplants. Allo-HCT patients who were administered palifermin had shorter time of mucositis (median: 9 vs. 13 days, p < 0.001), lower mucositis grade (median: 2° vs. 3°; p < 0.001), shorter period of total parenteral nutrition (median: 19 vs. 22 days; p = 0.018), and lower incidence of episodes of febrile neutropenia (median: 39.1% vs. 83.1%; p < 0.001).ConclusionsThe use of palifermin has decreased duration and severity of oral mucositis in children after allo-HCT. Palifermin is a safe and well-tolerated compound in children undergoing allo-HCT.

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