scholarly journals Impact of Cryopreservation and Transit Times of Allogeneic Grafts on Hematopoietic and Immune Reconstitution

2021 ◽  
Author(s):  
Katie Maurer ◽  
Haesook T Kim ◽  
Thomas Michael Kuczmarski ◽  
Heather M Garrity ◽  
Augustine Weber ◽  
...  
Keyword(s):  
Stem Cell ◽  
Clinical Outcomes ◽  
Graft Failure ◽  
Immune Reconstitution ◽  
White Blood Cells ◽  
Adverse Outcomes ◽  
T Cell Subsets ◽  
Unrelated Donor ◽  
Increased Risk ◽  
The Impact

We sought to evaluate the impact of cryopreservation of unrelated donor peripheral blood stem cell (PBSC) grafts on engraftment, chimerism, and immune reconstitution in the context of the Covid-19 pandemic. We reviewed stem cell product characteristics and clinical outcomes in 101 patients receiving cryopreserved PBSCs from unrelated donors (URD) between January 1, 2019, and December 31, 2020, compared with 203 patients receiving fresh URD PBSCs. We observed no differences in 6-month overall survival, progression free survival, or non-relapse mortality. Patients receiving cryopreserved PBSCs had delayed platelet engraftment and impaired reconstitution of white blood cells and T cell subsets at Day 30. Thirty-four percent of patients receiving cryopreserved grafts had CD3 chimerism <50% at Day 30 after transplantation, compared with 14% of patients receiving fresh PBSCs (p=0.0002). At day 100, this difference persisted (CD3+ chimerism <50%: 17% of cryopreserved cohort vs 6% of fresh cohort, p=0.016). Additionally, greater product age at infusion is associated with an increase in graft failure, independent of cryopreservation. Receipt of grafts >48 hours old at time of cryopreservation or infusion significantly increased the risk of graft failure (sHR =4.57 (95% CI 1.71-12.3), p=0.0025). Our data indicate that cryopreservation is associated with similar overall short-term clinical outcomes compared to fresh PBSC. However, patients must be monitored closely for increased risk of other potentially adverse outcomes including graft failure and poor immune recovery, particularly for grafts with older overall age at infusion. Longer term follow-up is needed to determine impact on relapse and survival.

scholarly journals Atrial fibrillation and clinical outcomes 1 to 3 years after myocardial infarction

Open Heart ◽  
2021 ◽  
Vol 8 (2) ◽  
pp. e001726
Author(s):  
Anthony P Carnicelli ◽  
Ruth Owen ◽  
Stuart J Pocock ◽  
David B Brieger ◽  
Satoshi Yasuda ◽  
...  
Keyword(s):  
Quality Of Life ◽  
Myocardial Infarction ◽  
Atrial Fibrillation ◽  
Clinical Outcomes ◽  
Oral Anticoagulants ◽  
Adverse Outcomes ◽  
Increased Risk ◽  
History Of ◽  
The Impact

ObjectiveAtrial fibrillation (AF) and myocardial infarction (MI) are commonly comorbid and associated with adverse outcomes. Little is known about the impact of AF on quality of life and outcomes post-MI. We compared characteristics, quality of life and clinical outcomes in stable patients post-MI with/without AF.Methods/resultsThe prospective, international, observational TIGRIS (long Term rIsk, clinical manaGement and healthcare Resource utilization of stable coronary artery dISease) registry included 8406 patients aged ≥50 years with ≥1 atherothrombotic risk factor who were 1–3 years post-MI. Patient characteristics were summarised by history of AF. Quality of life was assessed at baseline using EQ-5D. Clinical outcomes over 2 years of follow-up were compared. History of AF was present in 702/8277 (8.5%) registry patients and incident AF was diagnosed in 244/7575 (3.2%) over 2 years. Those with AF were older and had more comorbidities than those without AF. After multivariable adjustment, patients with AF had lower self-reported quality-of-life scores (EQ-5D UK-weighted index, visual analogue scale, usual activities and pain/discomfort) than those without AF. CHA2DS2-VASc score ≥2 was present in 686/702 (97.7%) patients with AF, although only 348/702 (49.6%) were on oral anticoagulants at enrolment. Patients with AF had higher rates of all-cause hospitalisation (adjusted rate ratio 1.25 [1.06–1.46], p=0.008) over 2 years than those without AF, but similar rates of mortality.ConclusionsIn stable patients post-MI, those with AF were commonly undertreated with oral anticoagulants, had poorer quality of life and had increased risk of clinical outcomes than those without AF.Trial registration numberClinicalTrials: NCT01866904.

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.

A Comparison of Stem Cell Source in Recipients of T-Cell Depleted Myeloablative Transplants for Leukaemia: No Difference in Mortality Using BM or PBSC.

Blood ◽  
2007 ◽  
Vol 110 (11) ◽  
pp. 46-46
Author(s):  
B.E. Shaw ◽  
Nigel H. Russell ◽  
A. Pagliuca ◽  
J. Apperley ◽  
G. Cook ◽  
...  
Keyword(s):  
Stem Cell ◽  
T Cell ◽  
Acute Gvhd ◽  
Chronic Gvhd ◽  
Unrelated Donor ◽  
Stem Cell Source ◽  
Increased Risk ◽  
Significant Difference ◽  
Cell Source ◽  
The Impact

Abstract The use of GSCF-mobilised Peripheral Blood Stem Cells (PBSC) for unrelated donor (UD) transplantation has increased dramatically since 2000. The association of PBSC with more rapid engraftment and with an increase in chronic Graft versus Host Disease (GvHD), compared to bone marrow (BM) has been reported in a number of studies. More recently the use of PBSC has been associated with an increase in transplant related mortality (TRM) and decrease in survival (OS) in T-cell replete transplants. We sought to analyse the impact of PBSC compared to BM in a cohort of UD transplant recipients, where T-cell depleting agents (in-vivo campath in >90%) were included in the transplant conditioning. The study included 145 patients transplanted between January 2000 and March 2006: CML- 35 in 1CP; acute leukaemia (AML in 61, ALL in 49)-110 in CR1 or 2. All had myeloablative conditioning regimens and received grafts with 9–10/10 matched HLA alleles. 86 patients received BM and 59 PBSC. There were no associations between the stem cell source and any transplant variable (including disease and stage). There was a trend to an increased use of PBSC in patients with a single antigen mismatch (p=0.052). All evaluable patients achieved neutrophil engraftment, with a significantly faster time to engraft in recipients of PBSC compared to BM (16 vs 20 days; p=0.0003). The incidence of acute GvHD was 46% (grade I in 50%, II in 41%, III in 8%, IV in 2%). This was significantly higher in recipients of PBSC (60%) compared to BM (36%; p=0.006), however there was no increase in either II/IV (p=0.69) or III/IV (p=0.18) disease in PBSC recipients. In univariate analysis, the presence of a single HLA mismatch (p=0.026) was the only other variable to be associated with an increase in acute GvHD. In a logistic regression model including both these variables, the use of PBSC remained significantly associated with an increase in aGvHD (OR=2.3; 95% CI 1.1,4.7;p=0.020). The TRM was 14%, 27% and 39% at 100 days, 1 and 5 years respectively. At none of these time points was the stem cell source associated with a significant difference in TRM. The 5-year incidence of chronic GvHD was 58% (BM 55%, PBSC 60%; NS), extensive disease in one third, and of relapse was 61% (BM 60%, PBSC 62%; NS). The 5-years OS was 41% with a median follow-up of 3.4 years (0.5–7.1). This was 44% using PBSC and 40% using BM (NS). In conclusion, although we observed an increase in acute GVHD with PBSC this was only of grade 1 disease. We found no association between the use of PBSC and an increased risk of chronic GVHD or of a worse transplant outcome, when compared to BM, in recipients of T-cell depleted myeloablative transplants for leukaemia.

Comparison of Clinical Outcomes and Day 30 Lymphocyte Recovery Between Two aGVHD Prophylaxis Regimens In Matched Unrelated Hematopoietic Stem Cell Transplant (MUD) Patients

Blood ◽  
2010 ◽  
Vol 116 (21) ◽  
pp. 2340-2340
Author(s):  
Zartash Gul ◽  
Mustafa Abdul-Hussein ◽  
Ivo Ditah ◽  
Joseph P. Uberti ◽  
Muneer H. Abidi ◽  
...  
Keyword(s):  
Stem Cell ◽  
Clinical Outcomes ◽  
Hematopoietic Stem Cell ◽  
Unrelated Donor ◽  
Cell Transplant ◽  
Hematopoietic Stem ◽  
Post Transplant ◽  
All Cause Mortality ◽  
The Impact ◽  
Cmv Status

Abstract Abstract 2340 Background: Compared to HLA related hematopoietic stem cell transplants (HSCT), matched unrelated donor transplant (MUD) is associated with higher rates of transplant related mortality (TRM), primarily due to a higher incidence of acute graft versus host disease (aGVHD) and infections. Several investigators have shown that early lymphocyte recovery predicts less TRM, overall morality, aGVHD, and relapse post transplant, in HLA matched related HSCT. Only Lablanc et al demonstrated that Lymphocyte recovery at day 30(L30) is associated with improved outcomes in MUD patients, with the use of antibody mediated in-vivo lymphocyte depletion. We sought to compare clinical outcomes, L30, and the ability of L 30 to predict clinical outcomes in two contemporaneous cohorts of MUD patients treated with two different regimens for aGVHD prophylaxis. Methods: We retrospectively evaluated all consecutive MUD patients at our institution, who received aGVHD prophylaxis regimen Mycophenolate Mofetil and Tacrolimus (MT) between January 2008 and June of 2010, {Group 1(Grp 1), N =70 }. The second group (Grp2, N=40) received Tacrolimus, Sirolimus and Thymoglobulin on phase II protocol (TST), between July 2008 and June 2010. Thymoglobulin was administered at a total dose of 4.5mg/kg on days -3,-2, & -1. Clinical outcomes and L30 were compared between the groups using chi square test. We evaluated the impact of L30 above or below 400/microliter (mic) on 6 month all cause mortality, TRM, relapse, aGVHD and infections in each group separately using log rank test. Results: Groups 1 and 2 were not significantly different with respect to age, CMV status and gender for both donor and recipient. Groups were unbalanced for hematological diagnosis. There was more advanced disease in Grp1 and more HLA mismatches in Grp2. Conditioning regimens included Busulphan/Fludarabine with or without Total Body Irradiation (TBI), Fludarabine/Melplan/TBI, Etoposide/TBI, Cytoxan/TBI, and Rituxan, Carmustine, Cytarabine, Etoposide and Melphan (R BEAM). The incidence of aGVHD (Grades I-IV) was significantly higher in Grp1 vs Grp2 (74% vs 26%, P=0.001). CMV reactivation, 6 months mortality and TRM were not significantly different between the 2 groups (P=0.58), (P=0.2), (P=0.26) respectively. A marginally significant increase in relapse was noted in Grp2 (P=0.046). Compared to Grp1, Grp2 had a significantly lower proportion of patients with L30 greater than 400/mic (Grp1 50% vs Grp2 74%, P=0.01). However this difference disappeared on day 60 (Grp1 67% vs Grp2 76% P=0.32), day 90 (Grp1 71% vs Grp2 75% P=0.66) and day 180 (Grp1 87% vs Grp 2 92% P=0.55) post transplant. More EBV reactivations occurred in Grp2 (20% vs 4%, P= 0.008). In a multivariate model, gender, CMV status, age (for both donor & recipient), and donors CD34+ counts, diagnosis at transplant, disease status at MUD and the degree of mismatch were not independent predictors of L30. In Grp 1, L30 above 400/mic was significantly associated with a lower all cause mortality (HR 0.2, CI= 0.06–0.82), lower TRM (HR=0.16, CI=0.042-0.61) at 6 months, and a non-significant decrease in the incidence of aGVHD (HR 0.6 CI 0.26–1.46). However, in Grp2 L30 above 400/mic was not associated with the same clinical outcomes. L30 (above or below 400/mic) was also not associated with CMV or EBV reactivation in either group. Conclusion: Compared to aGVHD prophylactic regimen MT, the use of triple immune suppression TST was associated with less aGVHD, and lower lymphocyte recovery at day 30 post transplant. L30 above 400/mic predicted less overall mortality and TRM at 6 months in Grp1. Further studies exploring recovery and kinetics of lymphocyte subsets may explain the difference in the ability of L30 to predict clinical outcomes between the two groups. Disclosures: Off Label Use: Bortezomib is currently not approved for maintenance therapy after Autologous stem cells transplant. Abidi: Millennium: Speakers Bureau. Lum: Transtarget Inc: Equity Ownership. Al-Kadhimi: Genzyme Pharmaceutical: Research Funding.

scholarly journals Association Between Furosemide Exposure and Clinical Outcomes in a Retrospective Cohort of Critically Ill Children

2021 ◽  
Vol 8 ◽  
Author(s):  
Xiaomei Dai ◽  
Jiao Chen ◽  
Wenjing Li ◽  
Zhenjiang Bai ◽  
Xiaozhong Li ◽  
...  
Keyword(s):  
Clinical Outcomes ◽  
Critically Ill ◽  
Urine Output ◽  
Conclusive Evidence ◽  
Adverse Outcomes ◽  
Critically Ill Children ◽  
Multivariate Logistic Regression Model ◽  
Fluid Accumulation ◽  
Increased Risk ◽  
The Impact

Furosemide is commonly prescribed in critically ill patients to increase the urine output and prevent fluid overload (FO) and acute kidney injury (AKI), but not supported by conclusive evidence. There remain conflicting findings on whether furosemide associates with AKI and adverse outcomes. Information on the impact of furosemide on adverse outcomes in a general population of pediatric intensive care unit (PICU) is limited. The aim of the cohort study was to investigate the associations of furosemide with AKI and clinical outcomes in critically ill children.Study Design: We retrospectively reviewed a cohort of 456 critically ill children consecutively admitted to PICU from January to December 2016. The exposure of interest was the use of furosemide in the first week after admission. FO was defined as ≥5% of daily fluid accumulation, and mean FO was considered significant when mean daily fluid accumulation during the first week was ≥5%. The primary outcomes were AKI in the first week after admission and mortality during PICU stay. AKI diagnosis was based on Kidney Disease: Improving Global Outcomes criteria with both serum creatinine and urine output.Results: Furosemide exposure occurred in 43.4% of all patients (n = 456) and 49.3% of those who developed FO (n = 150) in the first week after admission. Patients who were exposed to furosemide had significantly less degree of mean daily fluid accumulation than those who were not (1.10 [−0.33 to 2.61%] vs. 2.00 [0.54–3.70%], P < 0.001). There was no difference in the occurrence of AKI between patients who did and did not receive furosemide (22 of 198 [11.1%] vs. 36 of 258 [14.0%], P = 0.397). The mortality rate was 15.4% (70 of 456), and death occurred more frequently among patients who received furosemide than among those who did not (21.7 vs. 10.5%, P = 0.002). Furosemide exposure was associated with increased odds for mortality in a multivariate logistic regression model adjusted for body weight, gender, illness severity assessed by PRISM III score, the presence of mean FO, and AKI stage [adjusted odds ratio (AOR) 1.95; 95%CI, 1.08–3.52; P = 0.026].Conclusion: Exposure to furosemide might be associated with increased risk for mortality, but not AKI, in critically ill children.

Impact of the Ebola epidemic on clinical outcomes of HIV-infected soldiers and their dependents in Sierra Leone

2018 ◽  
Vol 30 (2) ◽  
pp. 106-112 ◽  
Author(s):  
Elizabeth Nagel ◽  
Michael J Blackowicz ◽  
Foday Sahr ◽  
Olamide D Jarrett
Keyword(s):  
Clinical Outcomes ◽  
Sierra Leone ◽  
Repeated Measures ◽  
Disease Outbreaks ◽  
Armed Forces ◽  
Hiv Treatment ◽  
Hiv Care ◽  
Increased Risk ◽  
The Republic ◽  
The Impact

The impact of the 2014–2016 Ebola epidemic in West Africa on human immunodeficiency virus (HIV) treatment in Sierra Leone is unknown, especially for groups with higher HIV prevalence such as the military. Using a retrospective study design, clinical outcomes were evaluated prior to and during the epidemic for 264 HIV-infected soldiers of the Republic of Sierra Leone Armed Forces (RSLAF) and their dependents receiving HIV treatment at the primary RSLAF HIV clinic. Medical records were abstracted for baseline clinical data and clinic attendance. Estimated risk of lost to follow-up (LTFU), default, and number of days without antiretroviral therapy (DWA) were calculated using repeated measures general estimating equations adjusted for age and gender. Due to missing data, 262 patients were included in the final analyses. There was higher risk of LTFU throughout the Ebola epidemic in Sierra Leone compared to the pre-Ebola baseline, with the largest increase in LTFU risk occurring at the peak of the epidemic (relative risk: 3.22, 95% CI: 2.22–4.67). There was an increased risk of default and DWA during the Ebola epidemic for soldiers but not for their dependents. The risk of LTFU, default, and DWA stabilized once the epidemic was largely resolved but remained elevated compared to the pre-Ebola baseline. Our findings demonstrate the negative and potentially lasting impact of the Ebola epidemic on HIV care in Sierra Leone and highlight the need to develop strategies to minimize disruptions in HIV care with future disease outbreaks.

scholarly journals Risk Factors for Primary and Secondary Graft Failure in Allogenic Hematopoietic Cell Transplantation: A Single Center Study

Blood ◽  
2019 ◽  
Vol 134 (Supplement_1) ◽  
pp. 2046-2046
Author(s):  
Zeyad Al-Shaibani ◽  
Eshrak AL-Shaibani ◽  
Mats Remberger ◽  
Wilson Lam ◽  
Arjun Law ◽  
...  
Keyword(s):  
Risk Factors ◽  
Stem Cell ◽  
Cumulative Incidence ◽  
Graft Failure ◽  
Hematopoietic Cell Transplantation ◽  
Donor Lymphocyte Infusion ◽  
Malignant Diseases ◽  
Single Center ◽  
Donor Chimerism ◽  
Increased Risk

Introduction: Allogeneic hematopoietic cell transplantation (allo-HCT) is a potentially curative therapy for high risk hematological diseases and sustained engraftment of the donor stem cells is essential for transplant success. Graft failure (GF) is a rare, but serious complication post allo-HCT. In the presented study we aimed to assess the incidence, risk factors in a single-center population and as well the impact on transplant outcome. Methods: Between 01 January 2015 and 31 December 2018, 557 patients underwent allo-HCT at our center. Data was collected retrospectively and updated in June 2019. Cases were included regardless of the underlying diagnosis, disease status prior to transplant, preparative regimen, or stem cell source. Primary graft failure was defined as failure to achieve an absolute neutrophil count (ANC) of >500/ µL by 28 days after bone marrow (BM) or peripheral blood stem cell (PB) transplantation. In contrast, secondary graft failure was defined as cytopenias after initial engraftment (ANC <500/µL), with (a) donor chimerism of less than 5% or (b) falling donor chimerism with intervention such as second transplant or donor lymphocyte infusion (DLI) or (c) patient death due to cytopenias, and fall in donor chimerism, even if chimerism was >5%. Exclusion criteria for diagnosis of GF were (a) disease relapse (b) graft versus host disease or (c) other causes of cytopenias such as, viral infections, or drug induced. Outcomes examined included overall survival (OS), cumulative incidence of GF, non-relapse mortality (NRM) and cause of death. Results: Baseline characteristics are summarized in (Table 1). GF was seen in 43 (7.7%) patients. Of these 43 patients, 9 (21%) had primary GF, and 34 (79%) had secondary GF. The cumulative incidence of GF overall (primary and secondary) is 1.6% (0.8- 3.0%) at day 100 and 6.5% (4.5-8.8%) at day 800. The median survival of patients following primary GF was 41 days versus 144 days in secondary GF. At one hundred days OS in primary GF was 22% and in secondary GF was 64%. The 1y and 2y OS for secondary GF was 33% and 28% respectively (Figure 1-A). Multivariable analysis demonstrated that the (a) diagnosis/transplant indication (MDS, myelofibrosis, lymphoma or non-malignant diseases) and (b) donor type (HLA-mismatched unrelated or haploidentical) were the only factors significantly associated with increased GF (Table 2). We determined the effect of more than one of these risk factors on the occurrence of graft failure as seen in (Figure 1-B). In the absence of any of the risk factors, the incidence of GF was 3.6%. If one risk factor was present, the incidence of GF was 9.9%, and if 2 risk factors were present, the incidence of GF was 24.5%. In primary GF, 5 patients underwent second allo-HCT. In secondary GF, 15 patients (44%) underwent a second allo-HCT and another 8 patients received donor lymphocyte infusion. All the patients with primary GF died because of graft failure and its associated complications. In secondary GF, 22 patients (51%) died, 30% of causes related to infections. Conclusions: Our study showed an increased risk for graft failure following the use of mismatched unrelated or haploidentical donors for diseases such as lymphoma, myelofibrosis, myelodysplastic syndrome and non-malignant diseases. As well, we found that a presence of two risk factors puts patients at clinically significant increased risk of graft failure. More intense conditioning therapy should be considered for patients with one but in particular two risk factors. Disclosures Michelis: CSL Behring: Other: Financial Support.

scholarly journals Results of Unrelated Donor Hematopoietic Stem Cell Transplantation for Sickle Cell Disease in Europe on Behalf of Paediatric Diseases (PDWP) and Inborn Errors Working Parties (IEWP) of the EBMT

Blood ◽  
2019 ◽  
Vol 134 (Supplement_1) ◽  
pp. 4583-4583 ◽  
Author(s):  
Eliane Gluckman ◽  
Josu de la Fuente ◽  
Barbara Cappelli ◽  
Graziana M. Scigliuolo ◽  
Fernanda Volt ◽  
...  
Keyword(s):  
Stem Cell ◽  
High Resolution ◽  
Hematopoietic Stem Cell Transplantation ◽  
Graft Failure ◽  
Median Number ◽  
Unrelated Donor ◽  
Cell Disease ◽  
Hla Matching ◽  
Hematopoietic Stem ◽  
Neutrophil Engraftment

Introduction: Allogeneic hematopoietic stem cell transplantation (HSCT) is, to date, the only curative treatment for sickle cell disease (SCD). Because a human leukocyte antigen (HLA) matched sibling donor is not always available, alternative stem cell sources such as unrelated or haploidentical related donors have been explored. The likelihood of finding a 10/10 (HLA-A, B, C, DRB1 and DQB1) matched donor varies among ethnic groups, with the lowest probability among individuals of African descent. To date, few series of SCD patients transplanted with an unrelated donor (UD) have been reported, but the high rates of rejection and chronic graft versus host disease (cGvHD) have limited its widespread application. Patients and methods: We report the results of a retrospective, registry based, survey on 70 UD HSCT performed in patients (pts) with SCD from UD in 22 European Society for Blood and Marrow Transplantation (EBMT) centers between 2005 and 2017. Data were collected from the EBMT database and missing information was updated by the centers. Median follow up was 38 (range 2-154) months. Most pts were HbSS (n=54; 78%), had positive serology for CMV (80%), and a Karnofsky score >80% (98%). Eighteen pts had a major ABO incompatibility. Recurrent vaso-occlusive crisis (n=58), cerebral vasculopathy (n=23) and acute chest syndrome (n=24) were the main indications for HSCT. Red blood cell (RBC) transfusions pre-HSCT were reported in 97% of pts of whom 53% received more than 20 transfusions; 14% of the transfused pts had RBC alloantibodies. Hydroxyurea pre-HSCT was used in 65% of pts. Median age at HSCT was 9.6 years (range 2-43) with 87% of pts being ≤ 16 years. Stem cell source was bone marrow (BM) in 55 pts (79%) and peripheral blood (PBSC) in 15 (21%). The median number of infused TNC /kg was 3.6 x 108 for BM and 7.1 x 108 for PBSC; the median number of infused CD34/kg was 4.4 x 106 for BM and 8.3 x 106 for PBSC. HLA matching at high resolution typing was 10/10 (HLA-A, B, C, DRB1 and DQB1) in 31, 9/10 in 17 and 8/10 in 4 of the patient-donor pairs; intermediate resolution typing was available for 10 (10/10 or 9/10) and the HLA information was missing for the remaining 8 patient-donor pairs. The most frequent conditioning regimens were fludarabine-thiotepa-treosulfan (64%) and busulfan- cyclophosphamide (12%). GvHD prophylaxis was cyclosporine plus methotrexate in 59%. Anti-thymocyte globulin was used in 90% and alemtuzumab in 9% of pts. Results: The cumulative incidence (CI) of neutrophil engraftment at 60 days was 93% (95% CI 76-100), with median time to engraftment of 18 days; platelet engraftment at 180 days was 90% (95% CI 83-98) with a median time of 20 days. Ten pts had graft failure (5 primary and 5 secondary) of whom 6 had a second transplant and were all alive at last FU (median 9.5 months after second HSCT). The CI of grade II-IV aGVHD at 100 days was 23% (95% CI 15-36), and 8 pts (11%) had grade III-IV. Acute GVHD was more frequent in patients who received PBSC (PBSC 42.9%, BM 18.2%, p=0.062). Three-year CI of cGVHD was 23% (95% CI 15-36), 7 pts (10%) had limited and 9 (13%) extensive cGvHD. Three-year overall survival (OS) was 90±4%; three-year event free survival (EFS) (considering death and graft failure as events) was 76±6%; HLA matching between donor and recipient was the most important factor for OS and EFS. Considering only pts-donor pairs with high resolution HLA typing available (n=52), 3-year OS was 96±4% in 10/10 group compared to 77±11% in 9/10 plus 8/10 group (p 0.065), 3-year EFS was 85±7% vs 62±12% (p 0.040), respectively. No significant differences between the groups were observed in CI of neutrophil engraftment, aGVHD and cGVHD. Conclusion: UD HSCT is a valid option for SCD patients who lack an HLA-identical sibling donor. Nevertheless, efforts are still needed to improve outcomes after UD HSCT. Our results indicate that using a 10/10 HLA matched UD improves both OS and EFS compared to donors with 1 or more mismatches; so, when such a matched unrelated donor is not found, using an haplo relative or an unrelated cord blood as donor source should be evaluated. A prospective trial is in preparation to evaluate the use of haploidentical donors for HSCT in SCD (EudraCT number: 2018-002652-33). Disclosures No relevant conflicts of interest to declare.

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