A Population-Based Cohort Study of Second Malignancies and Late Mortality in Children Treated by Allogeneic Stem Cell Transplantation for Hematological Malignancies

Endothelial cells are involved in the pathogenesis of acute graft-versus-host disease (GVHD) after allogeneic stem cell transplantation. These cells express several molecules that can be detected as biologically active soluble forms; serum levels of these molecules may thereby reflect the functional status of endothelial cells. Furthermore, acute GVHD is an inflammatory reaction and endothelial cells function as local regulators of inflammation. We therefore investigated whether differences in preconditioning/pretransplant serum levels of endothelium-expressed molecules (i.e., endocan, vascular cell adhesion molecule 1 (VCAM-1), and E-selectin) were associated with a risk of posttransplant GVHD. Our study should be regarded as a population-based study of consecutive and thereby unselected patients (n=56). Analysis of this pretreatment endothelium biomarker profile by unsupervised hierarchical clustering identified a subset of patients with increased early nonrelapse mortality. Furthermore, low endocan levels were significantly associated with acute GVHD in the liver and gastrointestinal tract, whereas high VCAM-1 levels were associated with acute GVHD in the skin only. Our study suggests that the preconditioning/pretransplant status of endothelial cells (possibly through altered trafficking of immunocompetent cells) is important for the risk and the organ involvement of later acute GVHD.

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Pulmonary function following allogeneic stem cell transplantation in childhood: A retrospective cohort study of 51 patients

Pediatric Transplantation ◽

10.1111/petr.12313 ◽

2014 ◽

Vol 18 (6) ◽

pp. 617-624 ◽

Cited By ~ 3

Author(s):

L. M. Madanat-Harjuoja ◽

S. Valjento ◽

K. Vettenranta ◽

M. Kajosaari ◽

T. Dyba ◽

...

Keyword(s):

Cohort Study ◽

Stem Cell ◽

Stem Cell Transplantation ◽

Pulmonary Function ◽

Cell Transplantation ◽

Allogeneic Stem Cell Transplantation ◽

Retrospective Cohort Study ◽

Retrospective Cohort

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Conventional versus reduced-intensity conditioning regimen for allogeneic stem cell transplantation in patients with hematological malignancies

European Journal Of Haematology ◽

10.1111/j.1600-0609.2004.00360.x ◽

2005 ◽

Vol 74 (2) ◽

pp. 144-151 ◽

Cited By ~ 54

Author(s):

D. Valcarcel ◽

R. Martino ◽

A. Sureda ◽

C. Canals ◽

A. Altes ◽

...

Keyword(s):

Stem Cell ◽

Stem Cell Transplantation ◽

Cell Transplantation ◽

Allogeneic Stem Cell Transplantation ◽

Hematological Malignancies ◽

Conditioning Regimen ◽

Reduced Intensity Conditioning ◽

Reduced Intensity Conditioning Regimen ◽

Reduced Intensity

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Pathways Through Relapses and Deaths of Children With Acute Lymphoblastic Leukemia: Role of Allogeneic Stem-Cell Transplantation in Nordic Data

Journal of Clinical Oncology ◽

10.1200/jco.2006.07.1225 ◽

2006 ◽

Vol 24 (36) ◽

pp. 5750-5762 ◽

Cited By ~ 37

Author(s):

Ulla M. Saarinen-Pihkala ◽

Carsten Heilmann ◽

Jacek Winiarski ◽

Anders Glomstein ◽

Jonas Abrahamsson ◽

...

Keyword(s):

Stem Cell ◽

Acute Lymphoblastic Leukemia ◽

Stem Cell Transplantation ◽

Cell Transplantation ◽

Allogeneic Stem Cell Transplantation ◽

Lymphoblastic Leukemia ◽

Population Based ◽

Pediatric Hematology ◽

Resistant Disease ◽

First Relapse

Purpose Our focus was on patients with pediatric acute lymphoblastic leukemia (ALL) who experienced relapse or died without becoming transplantation candidates. The purpose was to outline measures needed to improve the outcome. Patients and Methods We analyzed our population-based 20-year data on 3,385 Nordic children with ALL treated on Nordic Society for Pediatric Hematology and Oncology ALL protocols, and described the flow of these patients through relapses, remissions, and deaths as a result of toxicity, demonstrating where major patient losses occurred. Results In total, 854 patients (25%) had a first and 274 patients (8%) had a second ALL relapse. P for survival after the first relapse was .35 ± .02. The induction mortality (2.2%, primary; 10.3%, first relapse; 26.3%, second relapse) and remission mortality (1%, first complete remission [1CR]; 19%, second CR [2CR]) were significant; transplantation-related mortality (TRM) only represented 15% (69 of 459) of the deaths as a result of toxicity. Of the 766 patients entering 2CR, 29% underwent transplantation (P for survival, .46 ± .04), whereas 71% continued receiving chemotherapy (P for survival, .39 ± .02). Children with stem-cell transplantation indications in 2CR, if they did not undergo transplantation, generally died or had a second relapse. The patient groups that underwent transplantation in 1CR (n = 84), 2CR (n = 220), and ≥ 3CR (n = 62) represented different risk profiles. Those with allogeneic stem-cell transplantation (allo-SCT) in ≥ 3CR (P for survival, .37 ± .07) had an ALL and first relapse with favorable features. Conclusion Major patient losses occurred through mortality as a result of toxicity and resistant disease during the pathways before allo-SCT. After relapse, more patients were lost to mortality as a result of toxicity during conventional chemotherapy compared with TRM. After second relapse, the chance for rescue by allo-SCT in ≥ 3CR was minimal. The question of whether transplantation is recommended after ALL relapse should be carefully addressed, and more efficient relapse protocols should be launched.

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