Bojtarova E

Serial measurements of cardiac biomarkers in patients after allogeneic hematopoietic stem cell transplantation

BackgroundPrevious therapy with anthracyclines (ANT) and conditioning regimen followed by hematopoietic stem cell transplantation (HSCT) represents a high risk for development of cardiotoxicity. The aim of this study was to assess subclinical myocardial damage after HSCT using echocardiography and cardiac biomarkers - high sensitive cardiac troponin T (hs-cTnT) and N-terminal pro-B-type natriuretic peptide (NT-proBNP) and to identify patients at risk of developing clinical cardiotoxicity.Patients and methodsThirty-seven patients who were treated with allogeneic HSCT for hematologic diseases at median age of 28 years at time of HSCT were studied. Conditioning regimen included either chemotherapy without total body irradiation (TBI) or combination of chemotherapy with TBI. Twenty-nine (78,3%) patients were pretreated with ANT therapy. Cardiac biomarkers were serially measured before conditioning regimen and at days 1, 14 and 30 after HSCT. Cardiac systolic and diastolic functions were assessed before conditioning regimen and 1 month after HSCT by echocardiography.ResultsThe changes in plasma NT-proBNP and hs-cTnT levels during the 30 days following the HSCT were statistically significant (P < 0,01 v.s. P < 0,01). Persistent elevations of NT-proBNP and hs-cTnT simultaneously for a period exceeding 14 days after HSCT were found in 29,7% patients. Serum concentrations of cardiomarkers were significantly elevated in ANT group compared to non-ANT group. These observations were underscored by the echocardiographic studies which did reveal significant changes in systolic and diastolic parameters. Five of 37 (13,5%) patients developed clinical manifestation of cardiotoxicity.ConclusionsElevations in both cardiac biomarkers were found before clinical signs of cardiotoxicity developed. Persistent elevations in NT-pro-BNP and hs-cTnT concentrations simultaneously for a period exceeding 14 days might be used for identification of patients at risk of developing cardiotoxicity and requiring further cardiological follow up.

Treatment difficulty with acute GVHD - frequent cause of mortality after allogeneic hematopoietic stem cell transplantation.

OBJECTIVE Acute graft-versus-host disease (aGvHD) remains a significant cause of morbidity and mortality after allogeneic hematopoietic stem cell transplantation (HSCT). METHODS In this study, we have retrospectively evaluated the major risk factors for the development of aGvHD in 100 patients who underwent allogeneic transplantation at the University Hospital in Bratislava between January 2007 and December 2011. RESULTS 29 patients acquired acute GvHD (Grade I - 12 patients, G II - 5 , G III - 3, G IV - 9). We proved a higher incidence of developing aGvHD in patients with unrelated donor type, TBI conditioning and cyclosporine (CsA) replacement with mycophenolate mofetil due to CsA nephrotoxicity, while other risk factors such as older patient age, the use of peripheral blood progenitor cells and donor/recipient sex mismatch were without statistical significance. The average time of onset of aGvHD has been 57 days (range 13-260) after HSCT. Corticosteroids were used as standard initial therapy with 52 % complete response (CR) rate, although the likelihood of response rapidly decreased with increasing severity of disease (G IV - 100 % refracterness). The response to primary therapy also correlated with overall survival. Patients with steroid-refractory aGvHD received a different second-line therapies (antithymocyte globulin, anti-TNFα antibody, anti CD52 antibody) with response rate 45 % (CR - 18 %, PR - 27 %). CONCLUSION Outcome for the patients with steroid-refractory aGvHD was poor, disease very often returned or progressed with one year mortality rate 81 % , that represents an important therapeutic problem (Tab. 2, Ref. 10).

Abnormal cardiomarkers in leukemia patients treated with allogeneic hematopoietic stem cell transplantation.

OBJECTIVE Clinical cardiac complications in oncologic patients may develop from subclinical myocardial damage. Biomarkers N-terminal pro brain natriuretic peptide (NT-proBNP) and troponin T (cTnT) have been hypothesized to reflect preclinical cardiotoxicity earlier than echocardiography. The aim of this study was to assess prospectively the serial values of these cardiomarkers in leukemia patients treated with allogeneic hematopoietic stem cell transplantation (HSCT). PATIENTS Twenty-one patients who were treated with allogeneic HSCT for acute leukemia at mean age of 32.8 years (range: 19-58) were studied. The conditioning regimen included high-dose cyclophosphamide in combination with total body irradiation (TBI) or busulphan. All patients were treated with anthracyclines earlier (median cumulative dose 250 mg/m, range: 150-580). METHODS Cardiomarkers were measured before the preparative regimen (PR) and on days 1, 14 and 30 after HSCT. Their cardiac systolic function was assessed before PR, and 1-2 months after HSCT by echocardiography. RESULTS AND CONCLUSION The differences in NT-proBNP before PR and after HSCT were statistically significant (p<0.001). The values of cTnT before and after HSCT were also significantly different (p=0.005). Persistent abnormalities (30 days after HSCT) of NT-proBNP levels were found in 19/21 patients (90.5 %) and of cTnT levels in 10/21 patients (47.6 %). The median cTnT concentrations were higher in patients treated with TBI than in patients without TBI (p=0.013). The median NT-proBNP values were higher in patients pretreated with higher cumulative doses of anthracyclines (>250 mg/m vs ≤250 mg/m) Cardiac symptoms developed in 3/21 (14.3 %) patients (Tab. 1, Fig. 3, Ref. 36).

Graft-versus-host disease management.

Graft-versus-host disease (GVHD) remains a major problem of allogeneic hematopoietic-stem cell transplantation (HSCT) and an obstacle for successful outcome. Clinically significant acute GVHD (grade II or higher) developed in 20 to 65 percent of the patients. Death due to this complication accounts for approximately 50 percent of the deaths that are not due to a relapse of the neoplasm. Up to 70 % of patients who survive beyond day 100 develop chronic GVHD and it is the leading cause of nonrelapse mortality more than 2 years after allogeneic HSCT. In addition, chronic GVHD is associated with decreased quality of life, impaired functional status, and ongoing need for immunosuppressive medications. The incidence of chronic GVHD is increasing because of expansion of the donor population beyond HLA-identical siblings, older recipient age, use of peripheral blood cells as the graft source, and infusion of donor lymphocytes for treatment of recurrent malignancy after HSCT. With the current rush in new findings related to GVHD, we see a significant advancement in its management. Given these various new options and challenges, it is important to identify the minimal requirements for diagnosis and treatment of GVHD, as access to the most sophisticated advances may vary depending on local circumstances (Tab. 4, Fig. 1, Ref. 51).

Autologous hematopoietic stem cell transplantation for acute myeloid leukemia – single center experience

We aimed to determine the effect of autologous hematopoietic stem cell transplantation (auto-HSCT) on acute myeloid leukemia (AML) patients as a valid alternative therapeutic option for patients without HLA-compatible donor. This retrospective single center study included 79 patients with AML older than 18 years. In this report, we describe the patient characteristics, engraftment, toxicity of treatment, complications, overall survival, and relapse incidence of 79 patients treated chemotherapy and followed by auto-HSCT. The descriptive statistics was used, and the method of Kaplan and Meier was applied to calculate the actuarial rate of overall survival. The patients achieved an absolute neutrophile count (ANC) of ≥ 0.5 x109/l in between 10 to 40 days; median was 14 days after auto-HSCT. The patients achieved platelet count ≥ 20 x109/l in between 10 to 209 days; median was 19 days after auto-HSCT. Hundred-day mortality after autologous transplant was 6.57% (5/76). The relapse rate was 39.5% (32 patients) and 7 patients (8.6%) were lost from follow-up. On the date of evaluation (April 30, 2016), 48 patients (60.8%) were alive, including 7 (8.6%) patients who are lost from follow-up (not responding to check-up request). The 5-year overall survival (OS) was 60.8%; median overall survival was not reached. The present clinical study has demonstrated safety and efficacy of myeloablative chemotherapy followed by auto-HSCT in the treatment of AML in first remission.