scholarly journals “Giving the gift of life twice”: Understanding the lived experiences of parent donors and non-donors in pediatric haploidentical hematopoietic cell transplantation

2021 ◽  
Author(s):  
Megan Schaefer ◽  
Vanessa Aguilera ◽  
Kendra Parris ◽  
Alanna Long ◽  
Brandon Triplett ◽  
...  
Keyword(s):  
Cell Transplantation ◽  
Hematopoietic Cell Transplantation ◽  
Psychological Impact ◽  
Hematopoietic Cell ◽  
Unrelated Donor ◽  
Donation Process ◽  
The Gift ◽  
Haploidentical Hematopoietic Cell Transplantation ◽  
Level Of Understanding ◽  
The Impact

Background: The use of parental donors in pediatric haploidentical hematopoietic cell transplantation is increasing, but research on the psychosocial impact of parental donation is currently limited. We conducted a retrospective, qualitative study to explore parental perceptions of the donation process and the impact of being a donor (or non-donor) on parents’ adjustment and coping with their child’s transplant experience. Methods: Parents/caregivers of children who underwent transplantation with a parental donor or a matched unrelated donor (N = 136) participated in interviews and completed an open-ended questionnaire. Both bereaved parents and parents of survivors were surveyed. Results: Six themes were identified in the data: level of understanding and satisfaction; perception of choice; preparation for donation; perceptions of donation and infusion; benefit-finding; and psychological impact of transplantation. Most parents were satisfied with the information they received and reported a good understanding of transplantation and donation procedures. Parents were divided on perspectives of choice, but their responses reflect that the necessity of saving their child’s life does not allow for choice. They described considerable effort to prepare for transplantation, physically, emotionally, and logistically. Parents acknowledged the psychological impact while identifying positive outcomes that resulted from their child’s transplant journey. Conclusions: Results highlight the unique experiences of parental donors and non-donors from the anticipation phase to the completion of their child’s transplant. Additionally, findings inform supportive care guidance by highlighting the need to assess parental donors’ emotional functioning, provide support post-donation, and conduct bereavement follow-up.

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 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.

Impact of Pre-Transplant Minimal Residual Disease Assessed by Flow Cytometry on Outcome Following Myeloablative Hematopoietic Cell Transplantation for Patients with AML-CR1.

Blood ◽  
2008 ◽  
Vol 112 (11) ◽  
pp. 3253-3253 ◽  
Author(s):  
John M. Pagel ◽  
Ted Gooley ◽  
Elihu Estey ◽  
Brent Wood ◽  
Frederick R. Appelbaum
Keyword(s):  
Stem Cells ◽  
Flow Cytometry ◽  
Cell Transplantation ◽  
Hematopoietic Cell Transplantation ◽  
Residual Disease ◽  
Flow Cytometric Analysis ◽  
Hematopoietic Cell ◽  
Unrelated Donor ◽  
Number Of Patients ◽  
The Impact

Abstract Allogeneic hematopoietic cell transplantation (HCT) often offers the best and sometimes only chance for cure for acute myeloid leukemia (AML) patients. However, the decision of whether to transplant a patient with AML while in first remission remains a difficult one, and a great deal of attention has been given to attempting to identify factors that will predict HCT outcome. While many patient- and disease-specific factors have been studied, little attention has been given to the impact of the presence of MRD as determined by multiparametric flow cytometry (MFC) at the time of presentation for transplant on outcome. We have therefore evaluated outcome among patients transplanted for AML in CR1, comparing those with evidence of MRD as determined by MFC compared to those with no evidence of MRD prior to myeloablative HCT. Between 1992 and 2004, 140 patients greater than 18 years of age with AML-CR1 received a myeloablative HCT at our Center. Immediately prior to HCT, 23 CR1 patients had evidence of MRD (MRD+) whereas 117 CR1 patients had no evidence of MRD (MRD-) by flow cytometric analysis. Four (17%) MRD+ patients and 23 (20%) MRD- patients had an unrelated donor. Median age was 48.1 and 40.7 years for MRD+ and MRD- patients, respectively. Conditioning included use of total body irradiation (n=8 MRD+; n=37 MRD-), busulfan and cyclophosphamide (n=8 MRD+; n=42 MRD-), an anti-CD45 radiolabeled antibody (n=6 MRD+; n=34 MRD-), or other regimens (n=1 MRD+; n=4 MRD-). Most received cyclosporine and methotrexate for GvHD prophylaxis (96% MRD+; 97% MRD-). Source of stem cells was bone marrow in 39% MRD+ and 58% MRD- patients. Patients were further classified by cytogenetic risk as favorable (0% MRD+; 3% MRD-), intermediate (61% MRD+; 74% MRD-), or unfavorable (30% MRD+; 18% MRD-) (cytogenetics were missing for 2 MRD+ patients and 5 MRD- patients). At last follow-up, 16 (70%) MRD+ patients had died compared to 46 (39%) MRD- patients. Five-year estimates of overall survival were 35% and 64%, respectively. After adjusting for age, source of stem cells, donor, and unfavorable cytogenetics, the hazard ratio (HR) for mortality was 2.13 (95% CI 1.11–4.08, p=.02). Nine (39%) MRD+ patients relapsed after HCT compared to 25 (21%) MRD- patients and the 5-year estimates of relapse were 39% and 21%, respectively. The adjusted HR or relapse was 2.83 (1.19–6.73, p=.02). Thirty percent (n=7) of patients in the MRD+ group experienced transplant-related mortality (TRM) compared to 21% (n=25) in the MRD- group [adjusted HR=1.50 (0.54–4.19, p=.44)]. Among those who were MRD+, there was a positive correlation between the percentage of flow blasts and the risk of mortality and TRM. However, there was no suggestion of an association with relapse in this group. When modeling flow blasts as a continuous linear variable, each increase in flow blasts of 10% was associated with an increase in the hazard of mortality [HR=1.20 (1.00–1.45, p=.05)] and TRM [HR=1.39 (1.10–1.76, p=.006)], but not relapse [HR=0.77 (0.35–1.70, p=.51)]. While these data need to be confirmed in a larger number of patients, they suggest that any evidence of MRD+ at HCT by flow cytometry in AML-CR1 patients increases the risk of relapse and death after HCT relative to MRD- patients.

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.

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.

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