scholarly journals Elevated Pre Transplant Serum Ferritin is Associated With Increased Risk of Invasive Mold Infection (IMI) After Allogeneic Hematopoietic Stem Cell Transplantation (HSCT)

2011 ◽  
Vol 17 (2) ◽  
pp. S309
Author(s):  
S. Dadwal ◽  
B. Tegtmeier ◽  
I. James ◽  
S. Forman ◽  
V. Pullarkat
Keyword(s):  
Stem Cell ◽  
Hematopoietic Stem Cell Transplantation ◽  
Stem Cell Transplantation ◽  
Cell Transplantation ◽  
Hematopoietic Stem Cell ◽  
Serum Ferritin ◽  
Hematopoietic Stem ◽  
Increased Risk

scholarly journals Clonal hematopoiesis in donors and long-term survivors of related allogeneic hematopoietic stem cell transplantation

Blood ◽  
2020 ◽  
Vol 135 (18) ◽  
pp. 1548-1559 ◽  
Author(s):  
Steffen Boettcher ◽  
C. Matthias Wilk ◽  
Jochen Singer ◽  
Fabian Beier ◽  
Elodie Burcklen ◽  
...  
Keyword(s):  
Stem Cell ◽  
Hematopoietic Stem Cell Transplantation ◽  
Stem Cell Transplantation ◽  
Cell Transplantation ◽  
Hematopoietic Stem Cell ◽  
Hematopoietic Stem ◽  
Clonal Hematopoiesis ◽  
Increased Risk ◽  
Long Term Survivors

Abstract Clonal hematopoiesis (CH) is associated with age and an increased risk of myeloid malignancies, cardiovascular risk, and all-cause mortality. We tested for CH in a setting where hematopoietic stem cells (HSCs) of the same individual are exposed to different degrees of proliferative stress and environments, ie, in long-term survivors of allogeneic hematopoietic stem cell transplantation (allo-HSCT) and their respective related donors (n = 42 donor-recipient pairs). With a median follow-up time since allo-HSCT of 16 years (range, 10-32 years), we found a total of 35 mutations in 23 out of 84 (27.4%) study participants. Ten out of 42 donors (23.8%) and 13 out of 42 recipients (31%) had CH. CH was associated with older donor and recipient age. We identified 5 cases of donor-engrafted CH, with 1 case progressing into myelodysplastic syndrome in both donor and recipient. Four out of 5 cases showed increased clone size in recipients compared with donors. We further characterized the hematopoietic system in individuals with CH as follows: (1) CH was consistently present in myeloid cells but varied in penetrance in B and T cells; (2) colony-forming units (CFUs) revealed clonal evolution or multiple independent clones in individuals with multiple CH mutations; and (3) telomere shortening determined in granulocytes suggested ∼20 years of added proliferative history of HSCs in recipients compared with their donors, with telomere length in CH vs non-CH CFUs showing varying patterns. This study provides insight into the long-term behavior of the same human HSCs and respective CH development under different proliferative conditions.

The Impact of Center Experience on Results of Reduced Intensity – Allogeneic Hematopoietic Stem Cell Transplantation. A Survey From the Acute Leukemia Working Party (ALWP) of the European Group for Blood and Marrow Transplantation (EBMT)

Blood ◽  
2010 ◽  
Vol 116 (21) ◽  
pp. 3517-3517
Author(s):  
Sebastian Giebel ◽  
Myriam Labopin ◽  
Mohamad Mohty ◽  
Didier Blaise ◽  
Charles Craddock ◽  
...  
Keyword(s):  
Stem Cell ◽  
Hematopoietic Stem Cell Transplantation ◽  
Stem Cell Transplantation ◽  
Cell Transplantation ◽  
Hematopoietic Stem Cell ◽  
Hematopoietic Stem ◽  
Therapeutic Decisions ◽  
Increased Risk ◽  
The Impact ◽  
Reduced Intensity

Abstract Abstract 3517 Allogeneic hematopoietic stem cell transplantation with reduced intensity conditioning (RIC-HSCT) is increasingly applied for the treatment of patients with acute myeloid leukemia. However, the procedure is heterogeneous with no standards based on randomized trials being elaborated so far. Hence, particular therapeutic decisions are in major part based on individual experience. The goal of this study was to evaluate the impact of center experience on outcome of RIC-HSCT. Based on the registry of ALWP of the EBMT, we analyzed results of 1413 HLA-matched related (n=1058) or unrelated (n=355) transplantations performed in 203 European centers between 2001 and 2007. Only patients with AML in first complete remission were included. Median recipient age was 55 years (range, 18–77 y.). Centers were categorized by quintiles according to the number of RIC-HSCT procedures in a study period. The 2 years probability of leukemia-free survival (LFS) after RIC-HSCT performed in centers with the lowest activity (1st quintile, ≤ 15 procedures/7 years) equaled 43% compared to 55% in the remaining ones (p<0.001). The incidence of non-relapse mortality (NRM) was 24% and 15%, respectively (p=0.004). In a multivariate model adjusted for other potential prognostic factors low RIC-HSCT activity was associated with decreased chance of LFS (HR=0.69, p<0.001) as well as increased risk of NRM (HR=1.69, p=0.001) and relapse (HR=1.37, p=0.01). No significant differences were found between centers belonging to the 2nd -5th quintile. We conclude that center experience is a strong predictor of outcome and should be considered for future analyses evaluating results of RIC-HSCT. Disclosures: Off Label Use: Dasatinib as first line therapy in Ph ALL.

Malignancy Following Solid Organ and Hematopoietic Stem Cell Transplantation

2009 ◽  
Vol 02 ◽  
pp. 49
Author(s):  
Angela Susanne Punnett ◽  
Keyword(s):  
Stem Cell ◽  
Hematopoietic Stem Cell Transplantation ◽  
Stem Cell Transplantation ◽  
Cell Transplantation ◽  
Hematopoietic Stem Cell ◽  
Immunosuppressive Agents ◽  
Solid Organ ◽  
Hematopoietic Stem ◽  
Post Transplant ◽  
Increased Risk

There is a growing appreciation of the increased risk for malignancy following solid organ and hematopoietic stem cell transplantation as the survival of these patient populations increases overall. The risk for malignancy is related to a complex interaction of type, degree, and duration of immunosuppression, viral status, and recipient age. Most of the malignancies documented are common in the general population but occur with increasing incidence and have significant implications for post-transplant surveillance. Post-transplant lymphoproliferative disorder is specific to the transplant population and remains a treatment challenge. The development of novel immunosuppressive agents, the use of individualized immunosuppressive regimens, and collaborative therapeutic trials are necessary to advance clinical care for these patients. This article will review the current issues around malignancy in the post-transplant patient population.

Remuneration of hematopoietic stem cell donors: principles and perspective of the World Marrow Donor Association

Blood ◽  
2011 ◽  
Vol 117 (1) ◽  
pp. 21-25 ◽  
Author(s):  
Michael Boo ◽  
Suzanna M. van Walraven ◽  
Jeremy Chapman ◽  
Brian Lindberg ◽  
Alexander H. Schmidt ◽  
...  
Keyword(s):  
Stem Cell ◽  
Hematopoietic Stem Cell Transplantation ◽  
Stem Cell Transplantation ◽  
Cell Transplantation ◽  
Hematopoietic Stem Cell ◽  
The United States ◽  
Unrelated Donor ◽  
Hematopoietic Stem ◽  
Increased Risk ◽  
The World

Abstract Hematopoietic stem cell transplantation is a curative procedure for life-threatening hematologic diseases. Donation of hematopoietic stem cells (HSCs) from an unrelated donor, frequently residing in another country, may be the only option for 70% of those in need of unrelated hematopoietic stem cell transplantation. To maximize the opportunity to find the best available donor, individual donor registries collaborate internationally. To provide homogeneity of practice among registries, the World Marrow Donor Association (WMDA) sets standards against which registries are accredited and provides guidance and regulations about unrelated donor safety and care. A basic tenet of the donor registries is that unrelated HSC donation is an altruistic act; nonpayment of donors is entrenched in the WMDA standards and in international practice. In the United States, the prohibition against remuneration of donors has recently been challenged. Here, we describe the reasons that the WMDA continues to believe that HSC donors should not be paid because of ethical concerns raised by remuneration, potential to damage the public will to act altruistically, the potential for coercion and exploitation of donors, increased risk to patients, harm to local transplantation programs and international stem cell exchange, and the possibility of benefiting some patients while disadvantaging others.

Increased Incidence of Venous Thromboembolism Following Allogeneic Compared with Autologous Hematopoietic Stem Cell Transplantation.

Blood ◽  
2007 ◽  
Vol 110 (11) ◽  
pp. 3986-3986
Author(s):  
Andrew Gonsalves ◽  
Marc Carrier ◽  
Philip Wells ◽  
Sheryl McDiarmid ◽  
Lothar Huebsch ◽  
...  
Keyword(s):  
Stem Cell ◽  
Venous Thromboembolism ◽  
Hematopoietic Stem Cell Transplantation ◽  
Stem Cell Transplantation ◽  
Cell Transplantation ◽  
Hematopoietic Stem Cell ◽  
Central Venous Catheters ◽  
Central Venous ◽  
Hematopoietic Stem ◽  
Increased Risk

Abstract Background: The incidence of venous thromboembolism (VTE) following hematopoietic stem cell transplantation (HSCT) is not well described, particularly with the emerging trend towards increased ambulatory care in the transplant setting. HSCT involves high dose chemotherapy and/or radiation and is often associated with periods of immobilization. In addition, vascular damage and inflammation are common following transplantation and may further increase the risk of VTE. We sought to quantify the incidence of VTE in both allogeneic and autologous HSCT recipients and characterize the factors influencing these events. Methods: A retrospective analysis involving 589 patients (382 autologous, 207 allogeneic recipients undergoing transplantation between 2000–2005) was performed in order to identify the incidence of symptomatic acute deep proximal vein thrombosis (DVT) or pulmonary embolism (PE) in HSCT recipients. Only patients who provided signed informed consent regarding the utilization of their medical information for research purposes were included. All diagnostic imaging reports of CT pulmonary angiography, ventilation / perfusion (VQ) scanning and duplex ultrasound of the upper and lower extremities performed within the first year after HSCT were reviewed. A diagnosis of VTE was confirmed by reviewing the clinical record and verifying a moderate to high pre-test probability according to the Wells’ criteria. Non-catheter related events were the designated primary outcome. Symptomatic catheter-related events (superficial and deep veins) were secondary outcomes. Statistical analysis included comparison of mean values using Student’s t test and comparison of proportions using the chi squared analysis. Results: A total of 7 patients developed VTE following HSCT unrelated to central venous catheters (4 PE and 3 DVT) for an incidence of 1.2%. A total of 5 patients had VTE events in the allogeneic group (2.4%) and 2 autologous recipients suffered VTE events (0.52%, p=0.043). An increased number of PEs occurred in the allogeneic group compared with autologous recipients (4 vs 0, p=0.006). Symptomatic catheter-related thrombosis (superficial and deep venous occlusion combined) was not different between the allogeneic and autologous groups (7.25% vs. 5.50%, p= 0.4). Three allogeneic recipients (60%) had GVHD at the time of VTE diagnosis and only 1 patient had relapsing disease (20%) while both patients in the autologous cohort (100%) had progression of their disease at the time of VTE diagnosis. All VTE events unrelated to central venous catheters occurred after hematopoietic engraftment with a trend towards earlier occurrence in the allogeneic setting compared to autologous recipients (mean 153 days vs. 312 days, respectively, p=0.080). The mean platelet count at the time of VTE was 121 (50–174). Conclusion: HSCT patients have a high incidence of non-catheter related VTE compared to historical reports of the general and cancer populations. Allogeneic recipients have an increased risk of VTE and of PE in comparison to autologous transplant patients. VTE occurred exclusively in HSCT patients after hematopoietic recovery. Perhaps thrombocytopenia and the emphasis on ambulatory patient status in our program were protective against the development of VTE. Our study supports the notion that GVHD may contribute to the development of VTE in allogeneic transplant recipients. Moreover, progression of the underlying malignancy may be a dominant risk factor in the development of VTE in autologous recipients.

Role of Donor Clonal Hematopoiesis in Allogeneic Hematopoietic Stem-Cell Transplantation

2019 ◽  
Vol 37 (5) ◽  
pp. 375-385 ◽  
Author(s):  
Mareike Frick ◽  
Willy Chan ◽  
Christopher Maximilian Arends ◽  
Raphael Hablesreiter ◽  
Adriane Halik ◽  
...  
Keyword(s):  
Stem Cell ◽  
Hematopoietic Stem Cell Transplantation ◽  
Stem Cell Transplantation ◽  
Cell Transplantation ◽  
Hematopoietic Stem Cell ◽  
Cumulative Incidence ◽  
Chronic Gvhd ◽  
Hematopoietic Stem ◽  
Clonal Hematopoiesis ◽  
Increased Risk

Purpose Clonal hematopoiesis of indeterminate potential (CHIP) occurs in the blood of approximately 20% of older persons. CHIP is linked to an increased risk of hematologic malignancies and of all-cause mortality; thus, the eligibility of stem-cell donors with CHIP is questionable. We comprehensively investigated how donor CHIP affects outcome of allogeneic hematopoietic stem-cell transplantation (HSCT). Methods We collected blood samples from 500 healthy, related HSCT donors (age ≥ 55 years) at the time of stem-cell donation for targeted sequencing with a 66-gene panel. The effect of donor CHIP was assessed on recipient outcomes, including graft-versus-host disease (GVHD), cumulative incidence of relapse/progression (CIR/P), and overall survival (OS). Results A total of 92 clonal mutations with a median variant allele frequency of 5.9% were identified in 80 (16.0%) of 500 donors. CHIP prevalence was higher in donors related to patients with myeloid compared with lymphoid malignancies (19.2% v 6.3%; P ≤ .001). In recipients allografted with donor CHIP, we found a high cumulative incidence of chronic GVHD (cGVHD; hazard ratio [HR], 1.73; 95% CI, 1.21 to 2.49; P = .003) and lower CIR/P (univariate: HR, 0.62; 95% CI, 0.40 to 0.97; P = .027; multivariate: HR, 0.63; 95% CI, 0.41 to 0.98; P = .042) but no effect on nonrelapse mortality. Serial quantification of 25 mutations showed engraftment of 24 of 25 clones and disproportionate expansion in half of them. Donor-cell leukemia was observed in two recipients. OS was not affected by donor CHIP status (HR, 0.88; 95% CI, 0.65 to 1.321; P = .434). Conclusion Allogeneic HSCT from donors with CHIP seems safe and results in similar survival in the setting of older, related donors. Future studies in younger and unrelated donors are warranted to extend these results. Confirmatory studies and mechanistic experiments are warranted to challenge the hypothesis that donor CHIP might foster cGVHD development and reduce relapse/progression risk.

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