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1.
Int J Mol Sci ; 23(15)2022 Aug 06.
Article in English | MEDLINE | ID: covidwho-1994086

ABSTRACT

Non-relapse mortality due to GVHD and infections represents a major source of morbidity and mortality in pediatric HSCT recipients. Post-transplant cyclophosphamide (PTCy) has emerged as an effective and safe GVHD prophylaxis strategy, with improved GVHD and relapse-free survival in matched (related and unrelated) and mismatched haploidentical HSCT adult recipients. However, there are no published data in pediatric patients with acute myeloid leukemia who received matched-donor HSCT with PTCy. We demonstrate, in this case series, that the use of PTCy in this population is potentially safe, effective in preventing acute GVHD, does not impair engraftment, is associated with reduced non-relapse mortality, and does not hinder immune reconstitution post HSCT.


Subject(s)
Graft vs Host Disease , Hematopoietic Stem Cell Transplantation , Leukemia, Myeloid, Acute , Adult , Child , Cyclophosphamide/therapeutic use , Graft vs Host Disease/drug therapy , Graft vs Host Disease/etiology , Graft vs Host Disease/prevention & control , Humans , Leukemia, Myeloid, Acute/drug therapy , Recurrence , Retrospective Studies , Siblings , Unrelated Donors
2.
Vox Sang ; 117(9): 1121-1125, 2022 Sep.
Article in English | MEDLINE | ID: covidwho-1854205

ABSTRACT

BACKGROUND AND OBJECTIVES: Understanding changes in the demand and usage of unrelated allogeneic haematopoietic cell transplantation (HCT) donors during the COVID-19 pandemic is needed to optimize pandemic preparedness of registry and donor collection services. The aim of this study was to understand the extent to which the pandemic has impacted the demand and usage of unrelated donors and cord blood units (CBUs) at Canadian Blood Services (CBS). MATERIALS AND METHODS: Data regarding stem cell donor interest and product usage for unrelated allogeneic HCT were retrieved from the database at CBS using de-identified anonymous information. RESULTS: Unrelated donor searches for Canadian patients remained unchanged by the pandemic, reflecting stable demand. The number of unrelated allogeneic transplants performed within Canada also remained stable, while the number of cord blood transplants increased, chiefly for paediatric patients. Requests for donor verification typing, a first signal of potential interest, increased from domestic centres during the first 6 months of the pandemic and decreased from international centres, before returning to baseline levels. The proportion of transplants for Canadian patients who used stem cell products procured from Canadian donors increased between 3 and 6 months after the start of the pandemic before returning to baseline and appears to be increasing again more than 1 year after the start of the pandemic. Use of CBUs for Canadian paediatric patients increased and remains elevated. CONCLUSION: Demand for unrelated adult HCT donors has remained stable despite the evolving pandemic with a transient and recurring increased interest and usage of domestic adult donors. Use of CBUs for paediatric patients has increased and remains elevated. Registries and donor collection centres should maintain the capacity to expand services for domestic donor collection during pandemics to offset threats to international donor usage.


Subject(s)
COVID-19 , Hematopoietic Stem Cell Transplantation , Peripheral Blood Stem Cells , Adult , COVID-19/epidemiology , Canada/epidemiology , Child , Humans , Pandemics , Registries , Unrelated Donors
4.
Bone Marrow Transplant ; 56(10): 2489-2496, 2021 10.
Article in English | MEDLINE | ID: covidwho-1269382

ABSTRACT

Cryopreservation was recommended to ensure continuity of unrelated donor (UD) hematopoietic stem cell transplantation (HSCT) during COVID-19 pandemic. However, its impact on clinical outcomes and feasibility was not well known. We compared 32 patients who underwent UD HSCT using cryopreserved peripheral blood stem cells (PBSC) during the COVID-19 pandemic with 32 patients who underwent UD HSCT using fresh PBSC in the previous period. Median neutrophil engraftment was 17.5 and 17.0 days with cryopreserved and fresh grafts, respectively. Non-significant delays were found in platelet recovery days (25.5 versus 19.0; P = 0.192) and full donor chimerism days (35.0 and 31.5; P = 0.872) using cryopreserved PBSC. The rate of acute graft-versus-host disease at 100 days was 41% (95% CI [21-55%]) in cryopreserved group versus 31% (95% CI [13-46%]) in fresh group (P = 0.380). One-hundred days progression-relapse free survival and overall survival did not differ significantly. During COVID-19 pandemic, six frozen UD donations were not transfused and logistical and clinical issues regarding cryopreservation procedure, packaging, and transporting appeared. In summary, UD HSCT with cryopreserved PBSC was safe during this challenging time. More efforts are needed to ensure that all frozen grafts are transplanted and cryopreservation requirements are harmonized.


Subject(s)
COVID-19 , Graft vs Host Disease , Hematopoietic Stem Cell Transplantation , Cryopreservation , Hematopoietic Stem Cells , Humans , Pandemics , SARS-CoV-2 , Unrelated Donors
5.
Transplant Proc ; 53(8): 2498-2501, 2021 Oct.
Article in English | MEDLINE | ID: covidwho-1246217

ABSTRACT

The coronavirus disease 2019 pandemic has made us adjust our standards and cope with unpredictable circumstances affecting the whole world, including the medical field. A 2-year-old boy diagnosed with X-linked lymphoproliferative disease type 2 with concomitant positive polymerase chain reaction test for Epstein-Barr virus-DNA was admitted to our transplant ward. His treatment scheme had to be modified at the last moment because of a donor disqualification due to a positive polymerase chain reaction result for severe acute respiratory syndrome coronavirus 2 just before the apheresis. We decided to perform salvage haploidentical bone marrow transplant from the patient's mother because it was the only possible option. Now, in a 5-month observation period after the hematopoietic stem cell transplantation, our patient is in good general condition. His case convinced us to redirect our approach to transplant procedure preparation. Following the European Group of Blood and Marrow Transplantation recommendations, we use cryopreserved apheresis materials to ensure the availability of stem cell products before the start of a conditioning regimen.


Subject(s)
Bone Marrow Transplantation , COVID-19 , Epstein-Barr Virus Infections , Hematopoietic Stem Cell Transplantation , Lymphohistiocytosis, Hemophagocytic , Salvage Therapy , COVID-19/diagnosis , Child, Preschool , Graft vs Host Disease , Herpesvirus 4, Human , Humans , Lymphohistiocytosis, Hemophagocytic/surgery , Male , Stem Cells , Transplantation Conditioning , Unrelated Donors
7.
Transplant Cell Ther ; 27(3): 270.e1-270.e6, 2021 03.
Article in English | MEDLINE | ID: covidwho-1108498

ABSTRACT

SARS-CoV-2 has spread rapidly worldwide, but the full impact of the COVID-19 pandemic on the field of hematopoietic cell transplantation (HCT) remains unknown. To understand this better, an 18-item online survey was disseminated by the Worldwide Network for Blood & Marrow Transplantation with questions exploring SARS-CoV-2 testing algorithms, mobilization, and cryopreservation strategies and COVID-19 infections in allogeneic related and autologous hematopoietic progenitor cell (HPC) donors. The aim of this survey was to assess the impact of the outbreak on policies relating to HPC mobilization, collection, and processing with respect to changes in daily routine. A total of 91 individual responses from distinct centers in 6 continents were available for analysis. In these centers, the majority (72%) of allogeneic related and autologous donors are routinely tested for SARS-CoV-2 before HPC collection, and 80% of centers implement cryopreservation of allogeneic HPC grafts before commencing conditioning regimens in patients. Five related and 14 autologous donors who tested positive for COVID-19 did not experience any unexpected adverse events or reactions during growth factor administration (eg, hyperinflammatory syndrome). These data are limited by the small number of survey respondents but nonetheless suggest that centers are following the recommendations of appropriate scientific organizations and provide some preliminary data to suggest areas of further study.


Subject(s)
Bone Marrow Transplantation/statistics & numerical data , COVID-19/epidemiology , Hematopoietic Stem Cell Transplantation/statistics & numerical data , Pandemics , SARS-CoV-2 , Algorithms , Allografts , Bone Marrow Transplantation/trends , COVID-19/diagnosis , COVID-19/prevention & control , COVID-19 Testing/methods , COVID-19 Testing/statistics & numerical data , Cryopreservation/methods , Donor Selection/standards , Global Health , Health Care Surveys , Hematopoietic Stem Cell Mobilization/statistics & numerical data , Hematopoietic Stem Cell Transplantation/trends , Practice Patterns, Physicians'/statistics & numerical data , Procedures and Techniques Utilization/statistics & numerical data , Tissue Preservation/methods , Transplantation, Autologous , Unrelated Donors/statistics & numerical data
8.
Transplant Cell Ther ; 27(2): 133-141, 2021 02.
Article in English | MEDLINE | ID: covidwho-1108496

ABSTRACT

The impact of the coronavirus disease 2019 (COVID-19) pandemic on hematopoietic cell transplant (HCT) donor registries and transplant center (TC) practices is underreported. This article reports on the National Marrow Donor Program (NMDP) Be The Match Registry and its coordinating the provision of unrelated donor (URD) products to domestic and international TCs during the initial 3 months of the COVID-19 pandemic (March through May 2020). Specifically, NMDP data are presented for disease indications for transplant, URD search volumes and availability, graft requests and processing, courier utilization and performance, and conversion rates from formal donor search and workup to graft collection and shipment. Data following the onset of COVID-19 are compared to the immediate 3 months prior to the COVID-19 pandemic (December 2019 through February 2020) and the same quarter 1 year prior to COVID-19 (March through May 2019). During the initial onset of COVID-19 and compared to 1 year prior, TCs requested and the NMDP performed less donor searches. More multiple URD and direct to workup requests were processed by the NMDP, which likely reflected reductions in donor availability. Yet TCs continued to perform allogeneic transplants for acute disease indications like acute leukemia and myelodysplasia, using more cryopreserved grafts than before COVID-19. In comparison to prepandemic patient cycle conversion rates and durations, the NMDP was able to convert patient cycles at nearly the same or higher rates and in similar or shorter periods of time. Last, despite significant challenges caused by the pandemic, including interruptions in domestic courier services and travel restrictions, graft products were delivered to and received by TCs in similar periods of time than before COVID-19. Taken together, these data show that NMDP service line operations continued to function effectively during the early phases of the COVID-19 pandemic, ensuring requests for and delivery of URD products to domestic and international allogeneic HCT recipients.


Subject(s)
COVID-19/epidemiology , Hematopoietic Stem Cell Transplantation , Leukemia, Myeloid, Acute/therapy , Myelodysplastic Syndromes/therapy , Pandemics , SARS-CoV-2 , Unrelated Donors/supply & distribution , Humans , Registries , Transplantation, Homologous
10.
Biol Blood Marrow Transplant ; 26(7): e161-e166, 2020 07.
Article in English | MEDLINE | ID: covidwho-799190

ABSTRACT

With the COVID-19 pandemic and the ensuing barriers to the collection and transport of donor cells, it is often necessary to collect and cryopreserve grafts before initiation of transplantation conditioning. The effect on transplantation outcomes in nonmalignant disease is unknown. This analysis examined the effect of cryopreservation of related and unrelated donor grafts for transplantation for severe aplastic anemia in the United States during 2013 to 2019. Included are 52 recipients of cryopreserved grafts who were matched for age, donor type, and graft type to 194 recipients who received noncryopreserved grafts. Marginal Cox regression models were built to study the effect of cryopreservation and other risk factors associated with outcomes. We recorded higher 1-year rates of graft failure (hazard ratio [HR], 2.26; 95% confidence interval, 1.17 to 4.35; P = .01) and of 1-year overall mortality (HR, 3.13; 95% CI, 1.60 to 6.11; P = .0008) after transplantation of cryopreserved compared with noncryopreserved grafts, with adjustment for sex, performance score, comorbidity, cytomegalovirus serostatus, and ABO blood group match. The incidence of acute and chronic graft-versus-host disease did not differ between the 2 groups. Adjusted probabilities of 1-year survival were 73% (95% CI, 60% to 84%) in the cryopreserved graft group and 91% (95% CI, 86% to 94%) in the noncryopreserved graft group. These data support the use of noncryopreserved grafts whenever possible in patients with severe aplastic anemia.


Subject(s)
Anemia, Aplastic/therapy , Bone Marrow Transplantation/methods , Coronavirus Infections/epidemiology , Cryopreservation/methods , Graft Rejection/pathology , Graft vs Host Disease/pathology , Peripheral Blood Stem Cell Transplantation/methods , Pneumonia, Viral/epidemiology , Acute Disease , Adolescent , Adult , Aged , Anemia, Aplastic/immunology , Anemia, Aplastic/mortality , Anemia, Aplastic/pathology , COVID-19 , Child , Child, Preschool , Female , Graft Rejection/immunology , Graft Rejection/mortality , Graft vs Host Disease/immunology , Graft vs Host Disease/mortality , Histocompatibility Testing , Humans , Male , Middle Aged , Pandemics , Retrospective Studies , Siblings , Survival Analysis , Transplantation Conditioning/methods , United States/epidemiology , Unrelated Donors
14.
Biol Blood Marrow Transplant ; 26(7): 1312-1317, 2020 07.
Article in English | MEDLINE | ID: covidwho-208523

ABSTRACT

The COVID-19 pandemic has created significant barriers to timely donor evaluation, cell collection, and graft transport for allogeneic hematopoietic stem cell transplantation (allo-HCT). To ensure availability of donor cells on the scheduled date of infusion, many sites now collect cryopreserved grafts before the start of pretransplantation conditioning. Post-transplantation cyclophosphamide (ptCY) is an increasingly used approach for graft-versus-host disease (GVHD) prophylaxis, but the impact of graft cryopreservation on the outcomes of allo-HCT using ptCY is not known. Using the Center for International Blood and Marrow Transplant Research (CIBMTR) database, we compared the outcomes of HCT using cryopreserved versus fresh grafts in patients undergoing HCT for hematologic malignancy with ptCY. We analyzed 274 patients with hematologic malignancy undergoing allo-HCT between 2013 and 2018 with cryopreserved grafts and ptCY. Eighteen patients received bone marrow grafts and 256 received peripheral blood stem cell grafts. These patients were matched for age, graft type, disease risk index (DRI), and propensity score with 1080 patients who underwent allo-HCT with fresh grafts. The propensity score, which is an assessment of the likelihood of receiving a fresh graft versus a cryopreserved graft, was calculated using logistic regression to account for the following: disease histology, Karnofsky Performance Score (KPS), HCT Comorbidity Index, conditioning regimen intensity, donor type, and recipient race. The primary endpoint was overall survival (OS). Secondary endpoints included acute and chronic graft-versus-host disease (GVHD), non-relapse mortality (NRM), relapse/progression and disease-free survival (DFS). Because of multiple comparisons, only P values <.01 were considered statistically significant. The 2 cohorts (cryopreserved and fresh) were similar in terms of patient age, KPS, diagnosis, DRI, HCT-CI, donor/graft source, and conditioning intensity. One-year probabilities of OS were 71.1% (95% confidence interval [CI], 68.3% to 73.8%) with fresh grafts and 70.3% (95% CI, 64.6% to 75.7%) with cryopreserved grafts (P = .81). Corresponding probabilities of OS at 2 years were 60.6% (95% CI, 57.3% to 63.8%) and 58.7% (95% CI, 51.9% to 65.4%) (P = .62). In matched-pair regression analysis, graft cryopreservation was not associated with a significantly higher risk of mortality (hazard ratio [HR] for cryopreserved versus fresh, 1.05; 95% CI, .86 to 1.29; P = .60). Similarly, rates of neutrophil recovery (HR, .91; 95% CI, .80 to 1.02; P = .12), platelet recovery (HR, .88; 95% CI, .78 to 1.00; P = .05), grade III-IV acute GVHD (HR, .78; 95% CI, .50 to 1.22; P = .27), NRM (HR, 1.16; 95% CI, .86 to 1.55; P = .32) and relapse/progression (HR, 1.21; 95% CI, .97 to 1.50; P = .09) were similar with cryopreserved grafts versus fresh grafts. There were somewhat lower rates of chronic GVHD (HR, 78; 95% CI, .61 to .99; P = .04) and DFS (HR for treatment failure, 1.19; 95% CI, 1.01 to 1.29; P = .04) with graft cryopreservation that were of marginal statistical significance after adjusting for multiple comparisons. Overall, our data indicate that graft cryopreservation does not significantly delay hematopoietic recovery, increase the risk of acute GVHD or NRM, or decrease OS after allo-HCT using ptCY.


Subject(s)
Bone Marrow Transplantation/methods , Coronavirus Infections/epidemiology , Cryopreservation/methods , Graft vs Host Disease/prevention & control , Hematopoietic Stem Cell Transplantation/methods , Leukemia/therapy , Lymphoma/therapy , Myelodysplastic Syndromes/therapy , Pneumonia, Viral/epidemiology , Adult , Aged , Aged, 80 and over , COVID-19 , Cohort Studies , Cyclophosphamide/therapeutic use , Female , Graft vs Host Disease/immunology , Graft vs Host Disease/mortality , Graft vs Host Disease/pathology , Histocompatibility Testing , Humans , Leukemia/immunology , Leukemia/mortality , Leukemia/pathology , Lymphoma/immunology , Lymphoma/mortality , Lymphoma/pathology , Male , Middle Aged , Myelodysplastic Syndromes/immunology , Myelodysplastic Syndromes/mortality , Myelodysplastic Syndromes/pathology , Pandemics , Siblings , Survival Analysis , Transplantation Conditioning/methods , Transplantation, Homologous , United States/epidemiology , Unrelated Donors/supply & distribution
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