Risk factors for capillary leakage syndrome after bone marrow transplantation

358

386

Summary:During neutrophil recovery following hematopoietic stem cell transplantation, a constellation of symptoms and signs including fever, erythrodermatous skin rash, and noncardiogenic pulmonary edema often occur. These clinical findings have usually been referred to as engraftment syndrome, or, reflecting the manifestations of increased capillary permeability, capillary leak syndrome. While described most often following autologous stem cell transplantation, a similar clinical syndrome has been observed followed allogeneic stem cell transplantation. Distinction from graft-versus-host disease in the allogeneic setting however, has been difficult. Recent experience with non-myeloablative conditioning for stem cell transplantation, however, reveals that an engraftment syndrome independent of GVHD may occur. In some cases, this engraftment syndrome may be a manifestation of a host-versus-graft reaction (graft rejection). While cellular and cytokine interactions are believed to be responsible for these clinical findings, a distinct effector cell population and cytokine profile have not been defined. Engraftment syndromes are likely associated with an increased transplant-related mortality, mostly from pulmonary and associated multiorgan failure. Corticosteroid therapy is often dramatically effective for engraftment syndrome, particularly for the treatment of the pulmonary manifestations. A proposal for a more uniform definition of engraftment syndrome has been developed in order to allow for a reproducible method of reporting of this complication and for evaluating prophylactic and therapeutic strategies. Bone Marrow Transplantation (2001) 27, 893-898.

Section: Autologous Stem Cell Transplantationmentioning

confidence: 96%

mentioning

confidence: 99%

Engraftment syndrome following hematopoietic stem cell transplantation

Spitzer

2001

358

386

“…Early reports of capillary leak syndrome after allotransplants identified clinical outcomes used to diagnose ES. Nurberger et al 5 reported capillary leak syndome (unexplained weight gain 43% of baseline weight within 24 h of engraftment and unresponsive to furosemide therapy) was more common after allo-vs autotransplants. In contrast, Cahill et al 4 reported similar rates.…”

Section: Engraftment Syndromementioning

confidence: 99%

“…[1][2][3] Most data suggest ES results from a proinflammatory state caused by release of diverse cytokines and other mediators of inflammation. ES was previously referred to as capillary leak syndrome, 4,5 autoaggression syndrome (after autotransplants) 6,7 and (when severe) aseptic shock syndrome. 8 ES is described after umbilical cord blood transplants and auto-, allo-and syngeneic-transplants of blood cells and BM cells.…”

Section: Introductionmentioning

confidence: 99%

Engraftment syndrome: double-edged sword of hematopoietic cell transplants

Spitzer

2015

112

128

Engraftment syndrome (ES) after hematopoietic cell transplantation (HCT) is increasingly diagnosed. Common features include fever, pulmonary vascular leak, rash and organ dysfunction. Different diagnostic criteria likely account for the wide (7-90%) range of reported incidences. ES typically occurs within 4 days of granulocyte recovery although a recently described seemingly similar syndrome occurs 41 week before granulocyte recovery after umbilical cord blood cell transplants. Although the clinical manifestations of ES may be identical to those of acute GVHD, ES also has been well described in patients without acute GVHD. The data are conflicting as to whether ES is associated with a higher nonrelapse mortality and worse survival after HCT. The pathophysiology of ES is unclear, but endothelial injury and activated granulocytes in the setting of proinflammatory cytokines may be important. ES typically is self-limited, but, like acute GVHD, responds to corticosteroids. Because ES and acute GVHD may have overlapping features and response to therapy, these disease processes may often not be distinct events. Moreover, features of ES may overlap with those of drug-and radiation-induced toxicities and infection. Further research to better characterize the clinical spectrum and etiology of ES and to determine its relationship to GVHD is needed.

“…Other studies have also addressed the impact of risk factors on post-BMT complications. [6][7][8][9][10] During the past decades we have improved our ability to prevent and/or treat such complications, and transplantrelated mortality (TRM) has been considerably reduced 11 and delayed: in our HLA-identical sibling program TRM was 39% before 1990 (385 patients) and occurred at a median interval of 48 days from BMT (range 1-1230); TRM is currently 17% (333 patients) with a median interval from transplant of 103 days (range 8-1419) (P Ͻ 0.00001) (unpublished). Very few patients die before day +7: the 10th percentile is currently day 30, and the 75th percentile is day 202.…”

mentioning

confidence: 99%

Early predictors of transplant-related mortality (TRM) after allogeneic bone marrow transplants (BMT): blood urea nitrogen (BUN) and bilirubin

Bacigalupo

Oneto

Bruno

et al. 1999

Summary:Transplant-related mortality (TRM) following allogeneic bone marrow transplantation (BMT) remains a major concern and early identification of patients at risk may be clinically relevant. In this study we describe a predictive score based on bilirubin and blood urea nitrogen (BUN) levels on day +7 after BMT. The patient population consisted of 309 consecutive patients who underwent BMT from sibling (n = 263) or unrelated donors (n = 46) for hematologic disorders between December 1990 and December 1996. Of 27 laboratory tests taken on day +7 after BMT, serum bilirubin (P = 0.02) and BUN (P = 0.007) were found to be independent predictors of TRM in multivariate analysis. The median levels of bilirubin (0.9 mg/dl) and of BUN (21 mg/dl) were then used as a cut-off and a score of 1 was given for values equal/greater than the median. There were 216 patients with scores 0-1 (low risk) on day +7 (bilirubin Ͻ0.9 and/or BUN Ͻ21) and 93 patients with score 2 (high risk) (bilirubin у0.9 and BUN у21): the latter had more grade III-IV acute graft-versus-host disease (P = 0.03), slower neutrophil (P = 0.02) and slower platelet engraftment (P = 0.002). The actuarial 5 year TRM is 22% for low risk vs 44% for high risk patients (P = 0.0003). For HLA-identical siblings TRM is 20% vs 35% (P = 0.01), for unrelated donors it is 20% vs 65% (P = 0.01). Day +7 score was highly predictive of TRM on multivariate analysis (hazard ratio 1.9, P Ͻ 0.01), after adjustment for year of transplant (P Ͻ 0.00001), unrelated vs sibling donors (P = 0.001), patient age (P = 0.01) and diagnosis (P = 0.01). These results were validated on an independent group of 82 allogeneic BMT recipients in a pediatric Unit who showed an actuarial TRM of 16% for low risk vs 46% for high risk patients (P = 0.002). This study suggests that it may be possible to identify patients with different risks of TRM on day +7 after BMT: high risk patients could be Allogeneic bone marrow transplantation (BMT) is associated with considerable morbidity and mortality, and several studies have addressed the issue of risk factors for major single complications such as interstitial pneumonitis, 1 acute GVHD 2,3 and graft rejection: 4 patient variables (older age), donor variables (older age, parous female donors for male recipients, degree of HLA matching) and transplant variables (longer interval from diagnosis to transplant, intensive regimens), are among these. A study from the Seattle group has looked at risk factors for veno-occlusive disease of the liver, another important complication of allogeneic BMT 5 and found that early increments in serum bilirubin level and body weight were highly predictive. Other studies have also addressed the impact of risk factors on post-BMT complications. [6][7][8][9][10] During the past decades we have improved our ability to prevent and/or treat such complications, and transplantrelated mortality (TRM) has been considerably reduced 11 and delayed: in our HLA-identical sibling program TRM was 39% before 1990 (385 patients) and occurred at a...