Severe Donor Events after Allogeneic Hematopoietic Stem Cell Donation.

Blood ◽  
2007 ◽  
Vol 110 (11) ◽  
pp. 3276-3276 ◽  
Author(s):  
Jörg Halter ◽  
Yoshihisa Kodera ◽  
Alvaro Urbano Ispizua ◽  
Hildegard Greinix ◽  
Norbert Schmitz ◽  
...  
Keyword(s):  
Stem Cell ◽  
Hematological Malignancies ◽  
Incidence Rates ◽  
Similar Frequency ◽  
Hematopoietic Stem ◽  
Allogeneic Hsct ◽  
Hematopoietic Malignancies ◽  
Life Threatening ◽  
Stem Cell Donation ◽  
Observation Times

Abstract The risk for donors of allogeneic hematopoietic stem cells (HSC) by bone marrow (BM) or by peripheral blood (PB) harvest is generally considered negligible. Scattered reports of severe to life-threatening complications and a recent controversy on hematopoietic malignancies after GCSF administration for peripheral stem cell donation have challenged this opinion. Previous studies were limited by small numbers. In two consecutive retrospective surveys conducted in 2003 and 2006 amongst 338 allogeneic transplant centres from 38 European countries participating in the annual EBMT activity surveys, centres were asked to report all donor deaths, all severe adverse events (SAE’s), defined as occurring within 30 days and any hematological malignancy in a donor occurring after HSC donation. 262/338 teams (77.5%) responded to the first survey (1993–2002) and 169/262 (65%) centres replied to the second survey (2003–2005). The responding teams performed a total of 51’024 first allogeneic HSCT, 27’770 BM and 23’254 PB HSCT, which corresponds to 69% of all 73’947 first allogeneic HSCT reported during this time to EBMT. There were 5 donor deaths, 1 after BM and 4 after PB donation, an incidence of 0.98 per 10’000 donations (95% CI 0.32–2.29), 37 SAE’s (incidence 7.25/10’000 donations; 95% CI 5.11–9.99), 12 in BM (incidence 4.32/10000 donations; 95% CI 2.24–7.75) and 25 in PB donors (incidence 10.76/10’000 donations; 95% CI 6.97–15.85; p<0.02). In absolute numbers, there were 20 hematological malignancies occurring in donors (3.92/10’000 donations; 95% CI 2.39–6.05), 8 after BM (2.88/10’000 donations; 95% CI 1.24–5.68) and 12 after PB donation (5.16/10’000 donations; 95% CI 2.67–9.02; p = 0.3). Based on the different observation times, the incidence rates for developing hematological malignancies are 0.398 per 10’000 person-years for BM and 1.20 per 10’000 person-years for PB donation, resulting in a relative risk of 3.02 (95% CI 1.11–6.87, p=0.027). These data document a definitive risk for death, SAE’s and hematological malignancies with HSC donation. Deaths occur with similar frequency in both groups. SAE’s were more frequently reported after PB donation. The incidence rate for developing hematopoietic malignancies is higher after PB donation. These data clarify the recent controversy on HSC donation. They form a basis for donor counselling and underline the need for standardised donor follow up and international cooperation in order to define risk factors and to build up preventive measures.

Danapaloid Is Significantly Effective for the Prophylaxis of Hepatic Veno-Occlusive Disease after Allogeneic Hematopoietic Stem Cell Transplantation: A Cohort Study of 85 Children with Hematological Malignancies.

Blood ◽  
2008 ◽  
Vol 112 (11) ◽  
pp. 1122-1122
Author(s):  
Hirotoshi Sakaguchi ◽  
Sayoko Doisaki ◽  
Nao Yoshida ◽  
Hideki Muramatsu ◽  
Nobuhiro Watanabe ◽  
...  
Keyword(s):  
Risk Factor ◽  
Stem Cell ◽  
Hematopoietic Stem Cell Transplantation ◽  
Hematological Malignancies ◽  
Significant Risk ◽  
Significant Risk Factor ◽  
Hematopoietic Stem ◽  
Allogeneic Hsct ◽  
Treatment Related Mortality ◽  
Related Mortality

Abstract Background: Veno-occlusive disease (VOD) is one of the regimen related toxicities in the early phase of hematopoietic stem cell transplantation (HSCT). Therapeutic modality for established VOD is limited and severe VOD cause multiple organ failure mostly with fatal prognosis despite intensive supportive care. Therefore prophylaxis of VOD is very important to reduce the treatment related mortality (TRM) after HSCT. Danapaloid, a mixture of low molecular weight heparan, dermatan, and chondroitin sulfates, promotes higher anti-coagulant activity with lower bleeding tendency than heparin could have a possibility of the prevention of VOD after HSCT. Patients: Eighty-five children with hematological malignancies (42 in CR1, CR2 or CP1 and 43 at advanced stages) underwent allogeneic HSCT from 2002 to 2008 in our institution. Underlying diseases were ALL(n=46), AML(n=26), CML(n=1), MDS(n=6), and NHL(n=6). They received bone marrow (n=69) or cord blood(n=16) from matched related (n=20), mismatched related(n=8), matched unrelated(n=30) or mismatched unrelated(n=27) donors. For the prophylaxis of VOD, dalteparin was given to 47 patients who underwent HSCT from 2002 to 2005, and danapaloid was given to 38 patients after 2005. In addition to dalteparin or danapaloid, ursodeoxycholic acid, tocopherol acetate, and eicosapentaenoic acid were given to all patients. We defined former 47 patients as dalteparin group and latter 38 patients as danapaloid group. Design: In this study, we compared the incidence of VOD, treatment related mortality at day 100 (day100 TRM) and 2 year overall survival (OS) between danaparoid group and dalteparin group as historical control in 85 consecutive patients with allogeneic HSCT. Results: In our observation, 8 patients (7 in dalteparin group, and 1 in danaparoid group) had VOD by day +30 (median day+22, range day+11 to +28) after HSCT. The probability of developing VOD for all patients was 10% (95% CI: 1–31%). Seven of 8 patients with VOD died and their probability of 2yr OS was 13% (95% CI: 1–42%). Five patients developed &gt;grade3 bleeding (4 in dalteparin group, and 1 in danapaloid group) and there was no significant difference on the probability of severe bleeding between two groups (10% versus 3%, p=0.21). In multivariate analysis by Coxhazard proportional model, the significant risk factor for the development of VOD was &gt;2nd transplant (HR: 17.5, 95%CI: 1.86–165, p=0.012) and the significant favorable factor for development of VOD was administration of danapaloid (HR: 0.09, 95%CI: 0.01–0.85, p=0.036). In the analysis of 85 consecutive HSCT procedures, the probability of day100 TRM was 15% (95% CI: 3–34%) and that of 2yr OS was 69% (95% CI: 56–78%). As for day100 TRM, the significant risk factors were &gt;2nd transplant (HR: 8.73, 95%CI: 1.75–43.5, p=0.008), HLA disparity of &gt;1Ag (HR: 10.3, 95%CI: 1.71–62.5, p=0.011) and posttransplant plasma ATIII level of &lt;96% (HR: 4.68, 95%CI: 1.05–20.8, p=0.042). As for 2yr OS, the only significant risk factor was HLA disparity of &gt;1Ag (HR: 3.26, 95%CI: 1.15–9.26, p=0.026). The danaparoid group had no significant advantage to dalteparin group on day100 TRM (HR: 0.55, 95%CI: 0.10–3.05, p=0.50) and 2yr OS (HR: 0.58, 95%CI: 0.19–1.73, p=0.33). Conclusion: Our findings suggest that administration of danapaloid is promising for the prophylaxis of VOD without increasing hemorrhagic complications. Prospective randomized, controlled study is mandatory to prove these findings.

Posttransplantation Vaccination: Concepts Today and on the Horizon

Hematology ◽  
2011 ◽  
Vol 2011 (1) ◽  
pp. 299-304 ◽  
Author(s):  
Katayoun Rezvani
Keyword(s):  
Stem Cell ◽  
High Risk ◽  
Hematological Malignancies ◽  
Leukemia Cells ◽  
Antileukemic Activity ◽  
Histocompatibility Antigens ◽  
Hematopoietic Stem ◽  
Allogeneic Hsct ◽  
Minor Histocompatibility Antigens ◽  
Antitumor Immunotherapy

Abstract Allogeneic hematopoietic stem cell transplantation (allogeneic HSCT) remains a curative treatment for hematological malignancies resistant to other treatment approaches through the unique GVL effect. However, relapse remains a major cause of treatment failure after allogeneic HSCT for patients with high-risk hematological malignancies. Further improvements in exploiting the GVL effect to prevent relapse in high-risk leukemias while minimizing toxicity have focused on the use of targeted antileukemic immunotherapy. These strategies include methods to boost the GVL effect with leukemia vaccines or the adoptive transfer of leukemia-specific lymphocytes. Vaccines can be classified as those against defined antigens such as minor histocompatibility antigens (mHags) or leukemia-associated antigens (PR1, WT1, and BCR-ABL) and those that have broad “antileukemic” activity such as engineered irradiated leukemia cells or leukemia-derived dendritic cells (DCs). The unique posttransplantation milieu, which is characterized by lymphopenia, regulatory T-cell depletion, and the release of growth factors, provides a unique opportunity for effective antitumor immunotherapy and augmenting specific GVL responses. This review focuses on approaches to enhancimg the GVL response by combining allogeneic HSCT with vaccination.

Prevention of Graft-Versus-Host Disease (GVHD) with Tacrolimus after Allogeneic Grafting for Hematological Malignancies Following Sub-Myeloablative Conditioning.

Blood ◽  
2006 ◽  
Vol 108 (11) ◽  
pp. 5321-5321
Author(s):  
Joseph Fay ◽  
Giovanna Saracino ◽  
Edward Agura ◽  
Brian Berryman ◽  
Luis Pineiro ◽  
...  
Keyword(s):  
Stem Cell ◽  
Cumulative Incidence ◽  
Hematological Malignancies ◽  
Chronic Gvhd ◽  
Progression Free Survival ◽  
P Value ◽  
Hematopoietic Stem ◽  
Free Survival ◽  
Allogeneic Hsct ◽  
Post Transplant

Abstract Severe acute or chronic GVHD following allogeneic hematopoietic stem cell transplantation therapy (HSCT) has a deleterious effect on the successful treatment of hematological malignancies. We have retrospectively studied mycophenolate mofetil (MMF) and tacrolimus (FK) or cyclosporine (CSA) following allogeneic HCST in the prevention of GVDH and the induction of immune tolerance in 93 patients with hematological malignancies using non-myeolablative pre-transplant conditioning. In the current study, there were 35 patients with leukemia, 36 patients with lymphoma, 12 patients with myelodysplastic syndrome or a myeloproliferative disorder and 10 patients with multiple myeloma. There were 63 women and the median age was 42 (15–75) years. Twenty patients had relapsed after previous autologous or allogeneic HSCT and 45 patients were older than 59 years. The remaining patients had co-morbid medical conditions that precluded the use of chemotherapy/radiotherapy dose-intensive pre-conditioning. Conditioning prior to allogeneic HSCT (94 blood stem cell grafts and 1 marrow graft) was fludarabine (90 mg/m2 in three daily doses) and TBI (200cGy) in 86 patients, fludarabine (120 mg/m2 in 4 daily doses) and cyclophosphamide (50mg/kg) in 5 patients, and TBI (200 cGy) only in 4 patients. Forty-three patients received sibling and 50 unrelated grafts. Median follow-up post transplant is 3.0 (0.2–6.1) years. Five (5.3%) patients did not experience sustained hematological chimerism post-transplant. MMF and FK were administered to 33 recipients and MMF and CSA to 60 recipients. The dose and schedule of MMF, CSA and FK have been published (Laport et al. Blood, 2006 and Fay et al. Blood, 1996.) There was no difference in the degree of HLA mismatching between the two groups of patients. Cumulative incidences were used to estimate the incidence of acute and chronic GVHD, all deaths and disease progressions not related to GVHD being considered as the competing events. The Gray test was used to compare cumulative incidences between groups. The unadjusted cumulative incidence of grade III–IV acute GVHD that required oral or systemic corticosteroid therapy, was 54% (95% CI, 40%–68%) in evaluable patients who received CSA in contrast to 38% (95% CI, 18%–58%) in patients who received FK (p-value=0.25). Furthermore, the unadjusted cumulative incidence of extensive chronic GVHD at 1 year was 45% (95% CI, 32%–58%) for CSA versus 34% (95% CI, 14%–54%) for FK (p-value=0.48). Progression-free survival between patients who received FK or CSA at the time of the analysis of this study is similar (p-value=0.6191). The progression-free survival at 1 year was 43% (95% confidence interval [CI], 24%–62%) for CSA versus 43% (95% CI, 31%–55%) for FK. Analyses of the overall morbidity and the incidence of infectious complications between the 2 groups are ongoing. FK combined with MMF may be superior to CSA and MMF in the prevention of GVHD post sub-myeloablative allogeneic HSCT therapy for hematological malignancies and FK may result in improvement of treatment outcome. We believe further study is warranted.

scholarly journals Endothelial cell dysfunction: a key determinant for the outcome of allogeneic stem cell transplantation

2021 ◽  
Author(s):  
Thomas Luft ◽  
Peter Dreger ◽  
Aleksandar Radujkovic
Keyword(s):  
Stem Cell ◽  
Stem Cell Transplantation ◽  
Cell Transplantation ◽  
Current Status ◽  
Sinusoidal Obstruction Syndrome ◽  
Hematopoietic Stem ◽  
Cell Dysfunction ◽  
Management Of Complications ◽  
Life Threatening

AbstractAllogeneic hematopoietic stem cell transplantation (alloSCT) carries the promise of cure for many malignant and non-malignant diseases of the lympho-hematopoietic system. Although outcome has improved considerably since the pioneering Seattle achievements more than 5 decades ago, non-relapse mortality (NRM) remains a major burden of alloSCT. There is increasing evidence that endothelial dysfunction is involved in many of the life-threatening complications of alloSCT, such as sinusoidal obstruction syndrome/venoocclusive disease, transplant-associated thrombotic microangiopathy, and refractory acute graft-versus host disease. This review delineates the role of the endothelium in severe complications after alloSCT and describes the current status of search for biomarkers predicting endothelial complications, including markers of endothelial vulnerability and markers of endothelial injury. Finally, implications of our current understanding of transplant-associated endothelial pathology for prevention and management of complications after alloSCT are discussed.

scholarly journals Should the BCRA1/2-mutations healthy carriers be valid candidates for hematopoietic stem cell donation?

2021 ◽  
Vol 19 (1) ◽  
Author(s):  
Alberto Fresa ◽  
Simona Sica
Keyword(s):  
Hematological Malignancies ◽  
Conditioning Regimen ◽  
Stress Factors ◽  
Brca Mutations ◽  
Hematopoietic Stem ◽  
Mutational Status ◽  
Stem Cell Donation ◽  
Radiation Treatments ◽  
Healthy Carriers

AbstractIt’s still not clear whether the mutational status of BRCA-mutated healthy hematopoietic stem cells (HSCs) donors could have an impact on the engraftment. Comparing the studies present in literature, we focused on the correlation between BRCA mutations and the development of hematological malignancies and Fanconi anemia (FA); then, we explored HSCs types, frequencies, and functions in the presence of BRCA mutations, as well as the reconstitution of hematopoiesis after chemotherapy and radiation treatments. The role of BRCA mutations in the FA showed a possible involvement in the onset of the disease; the mutation carriers, indeed, did not show any sign of the typical phenotype of the FA. BRCA mutational status can be considered as a risk factor for hematological malignancies, but only for secondary malignancies and/or in the presence of bone marrow stress factors. Currently we don’t know if a conditioning regimen could be compensated by BRCA mutated HSCs, even if murine models tried to show the possible differences between fully mutated, haploinsufficient and normal HSCs. Thus, given the downregulating effect of the mutations on hematopoiesis, it could be questionable to use the HSCs of a BRCA-mutated donor in the presence of another available donor with the same compatibility.

scholarly journals A Study on Hematopoietic Stem Cell Donation Volunteer Retention between Swab Sampling Approach and Blood Sampling Approach: Evidence from Shanghai, China

2021 ◽  
Vol 18 (8) ◽  
pp. 4027
Author(s):  
Ke Yan ◽  
Gang Zhang ◽  
Guoqiang Zhao ◽  
Baosong Liu ◽  
Jun Lu
Keyword(s):  
Stem Cell ◽  
Blood Sample ◽  
Hematopoietic Stem Cell ◽  
Blood Sampling ◽  
Distribution Characteristics ◽  
Hematopoietic Stem ◽  
Volunteer Retention ◽  
Sample Group ◽  
Stem Cell Donation ◽  
Sampling Approach

The loss of hematopoietic stem cell donation (HSCD) volunteers is widespread worldwide. This study analyzed the distribution characteristics of volunteer retention between the swab sampling approach and blood sampling approach. The Shanghai branch of the China Bone Marrow Donation Program conducted a telephone follow-up with 18,963 volunteers to understand volunteer retention. Multiple logistic regression was used to analyze the distribution characteristics of volunteer retention between two different sampling approaches, and a forest plot was used to observe the distribution trend. Only 32.37% of the volunteers could be contacted, and the loss of volunteers was severe. The volunteer retention is influenced by sampling approaches and demographic characteristics, and Shanghai natives, the highly educated, and students had better retention. The volunteer retention of the swab group was better among young people and technicians, while the volunteer retention of the blood sample group was lower among public officials and workers, and the volunteer retention in the blood sample group was more significantly affected by changes in population characteristics. To enhance the stability of volunteers, managers should improve the contact channels and frequency, expand the ratio of stable volunteers, strengthen volunteer education in the process of collecting blood samples, and respect individuals’ willingness.

scholarly journals Health-Related Quality of Life Following Allogeneic Hematopoietic Stem Cell Transplantation

Hematology ◽  
2010 ◽  
Vol 2010 (1) ◽  
pp. 248-254 ◽  
Author(s):  
Margaret Bevans
Keyword(s):  
Quality Of Life ◽  
Stem Cell ◽  
Clinical Practice ◽  
Hematopoietic Stem Cell Transplantation ◽  
Health Related Quality ◽  
Hematopoietic Stem ◽  
Allogeneic Hsct ◽  
Related Quality ◽  
Health Related

Abstract It is common knowledge that an allogeneic hematopoietic stem cell transplantation (HSCT) will have an enormous impact on the lives of transplant recipients and their families. Once an appropriate donor is identified, the curative potential of this treatment often drives the decision to proceed knowing that there will be intense physiologic toxicities and adverse effects on health-related quality of life (HRQL). Twenty-five years ago, HRQL was identified as an efficacy parameter in the evaluation of new anticancer drug therapy. Overall, the evidence suggests that an allogeneic HSCT has a significant impact on the overall HRQL of recipients, which is a result of decrements across all dimensions, including a significant symptom profile. The degree of impact on overall HRQL and the multiple dimensions varies across the transplant trajectory. Specific HRQL dimensions, such as physical function and symptoms, are easily incorporated into a clinician's assessment whereas other dimensions (eg, psychosocial) are less commonly integrated. The translation of HRQL results to improve clinical practice is not well established. Clinicians are often uncertain when to assess the scope of HRQL and how to interpret the information in a clinically meaningful way. The purpose of this review is to highlight the quality-of-life effects of allogeneic HSCT and discuss application into clinical practice.

scholarly journals Pharmacokinetics and Safety of Intravenous Cidofovir for Life-Threatening Viral Infections in Pediatric Hematopoietic Stem Cell Transplant Recipients

2015 ◽  
Vol 59 (7) ◽  
pp. 3718-3725 ◽  
Author(s):  
Amy E. Caruso Brown ◽  
Mindy N. Cohen ◽  
Suhong Tong ◽  
Rebecca S. Braverman ◽  
James F. Rooney ◽  
...  
Keyword(s):  
Stem Cell ◽  
Hematopoietic Stem Cell ◽  
Half Life ◽  
Viral Infections ◽  
Multiorgan Failure ◽  
Kidney Injury ◽  
Cell Transplant ◽  
Open Label ◽  
Hematopoietic Stem ◽  
Life Threatening

ABSTRACTChildren undergoing hematopoietic stem cell transplantation (HSCT) are at risk for life-threatening viral infections. Cidofovir is often used as a first-line agent for adenovirus infections, despite the absence of randomized controlled trials with HSCT patients, and as a second-line agent for resistant herpesvirus infections. The frequency and severity of adverse effects, particularly nephrotoxicity, in pediatric HSCT recipients are unclear, and pharmacokinetics (PK) of cidofovir in children have not previously been reported. This study was an open-label, nonrandomized, single-dose pilot study to determine the safety and PK of cidofovir in pediatric HSCT recipients with symptomatic adenovirus, nucleoside-resistant cytomegalovirus (CMV) or herpes simplex virus (HSV), and/or human papovavirus infections. Subsequent dosing and frequency were determined by clinical response and side effects, as assessed by the treating physician. Blood and urine samples were obtained from patients for PK studies and assessment of toxicity and virologic response. Twelve patients were enrolled (median age, 9 years; 33.5 days posttransplantation). Four of seven patients with adenovirus infection were successfully treated and eventually cleared their infections. Four of twelve patients died of disseminated viral disease and multiorgan failure. Two of twelve patients had evidence of acute kidney injury after the first dose, and one of these patients developed chronic kidney disease; two other patients developed late nephrotoxicity. The mean drug half-life was 9.5 h. There was no correlation between nephrotoxicity and plasma maximum concentration, clearance, or half-life. PK were similar to those reported for adults, although the drug half-life was significantly longer than that for adults. Cidofovir was well tolerated in the majority of patients. However, effective therapeutic strategies are urgently needed to support patients until immune reconstitution is achieved.

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