Graft-versus-host disease management Mistrik, M; Bojtarova, E; Sopko, L ...
Bratislavské lékarské listy,
2016, Volume:
117, Issue:
7
Journal Article
Peer reviewed
Open access
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).
Acute graft-versus-host disease (aGvHD) remains a significant cause of morbidity and mortality after allogeneic hematopoietic stem cell transplantation (HSCT).
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.
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 %).
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).
Hematopoietic stem cell transplantation (HSCT) offers patients with malignant and nonmalignant diseases the oportunity to pursue life-prolonging therapy. The number of survivors after successful HSCT ...is continually increasing. However, HSCT can induce tissue and organ damage that occurs not only "on treatment" , but long after completing therapy. Secondary malignancies belong to serious late complications after HSCT. A significant association of certain risk factors with increased likelihood of secondary malignancies after HSCT has been published over the last ten years. Better knowledge of pathogenesis of these complications, their early identification and treatment may contribute to better health outcomes of allogeneic and autologous hematopoietic stem cell transplantation recipients. We review here the incidence and risk factors of secondary malignancies after hematopoietic stem cell transplantation.
the role of autologous stem cell transplantation (ASCT) in treatment of acute myeloid leukemia (AML) remains unsettled.
retrospective analysis to evaluate the role of ASCT in patients with AML ...without HLA-matched donor.
between December 19, 1994 and August 1, 2012, a total of 63 patients with AML without HLA-matched donor in the department of Hematology and Transfusion Medicine, University Hospital, Bratislava, received an ASCT. Median age was 41 years (20-61 years). There were 35 (56%) males and 28 (44%) females. At the time of ASCT, 50 (79%) patients were in first complete remission (CR), 11 (18%) patients were in second CR and 2 (3%) patients were in relapse.
with a median follow-up of 115 months (34-214 months), the 10 year overall survival (OS) and disease free survival (DFS) of all patients was 55% and 51%, respectively. Transplant-related mortality was 6%. The relapse rate was 38% and 9 years probability of relapse was 44%.
ASCT is still an effective post-remission treatment in AML patients without HLA-matched donor; with the possibility of long-term survival or even cure in remarkable proportion of patients with AML, particularly in patients with favorable and intermediate cytogenetic risk. .
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).
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).
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.
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).
Isolated extramedullary relapse (IEMR) of acute leukemia (AL) after allogeneic bone marrow transplantation (BMT) is a rare occurrence. It is seen more commonly after BMT than after conventional ...chemotherapy (CHT) alone. We describe the natural history and response to treatment in four patients with IEMR following allogeneic BMT. The results indicate a stronger graft-versus-leukemia (GVL) effect in the marrow than in the peripheral tissues (Fig. 4, Ref. 13). Full Text (Free, PDF) www.bmj.sk.
We describe the implementation, optimization, sensitivity determination and first clinical results of polymerase chain reaction (PCR) amplification of polymorphic short tandem repeat (STR) markers ...and Amelogenin locus coupled with fluorescent detection and capillary electrophoresis in chimerism monitoring of patients transplanted at three different transplant centers using a commercially available multiplex microsatellite assay. The chimerism analysis was performed with genomic DNA extracted from unselected peripheral blood leukocytes of one hundred pediatric and adult patients, who underwent allogeneic stem cell transplantation (SCT) from human leukocyte antigen (HLA) matched or one antigen mismatched related or unrelated donors for malignant (70 patients) and non-malignant (30 patients) diseases. Tested were 79 donor recipient pairs for 15 STR systems and identified an informative marker in all but one of them (98,7%), using 6 selected systems out of these fifteen, that appeared highly informative in our patients population. In 21 sex-mismatched donor recipient pairs we used the Amelogenin locus to distinguish the X and Y chromosome. In sixty-three out of these 100 patients chimerism was regularly analyzed from blood samples taken at various time points after SCT with the median follow up of 17 months. Complete chimerism (CC), maintained over the whole follow-up period, was detected in 24 (38, 1%), stable and decreasing mixed chimerism (MC) in 28 (44, 4%) and increasing MC in 11 patients (17, 5%). Patients with CC, stable and decreasing MC showed a significantly better (p 0,005) overall survival rate (0, 81), compared to those with increasing MC (0, 24). These results demonstrate that STR-based chimerism monitoring with sensitivity above 1% and high informativity (98, 7% of donor recipient pairs) is necessary in establishing the origin of engrafted cells after an allogeneic SCT, in detecting graft rejection and that it may contribute in identifying patients with imminent leukemia relapse.
Allogeneic hematopoietic stem cell transplantation (alloHSCT) is a substantial therapeutic procedure for the treatment of a wide spectrum of severe diseases. Despite advancements in treatment and ...supportive care, alloHSCT still carries a considerable mortality risk, primarily caused by graft-versus-host disease (GvHD). Our retrospective analysis aimed to identify the factors influencing overall survival and GvHD development in HLA-identical sibling alloHSCT. We have analyzed patients' and donors' age, AB0 compatibility, recipient-donor gender match, stem cell source, time from the diagnosis to alloHSCT, conditioning regimen type, GvHD prophylaxis, and relapse.
Our study included 96 patients (54 male, 42 female) who underwent HLA-identical sibling alloHSCT. The median follow-up was 64.5 months (range 1-218 months), and the median age of both recipients and donors was 34 years. Malignant hematological diseases were the most common indications for alloHSCT.
GvHD and its complications accounted for the highest number of deaths (N = 24; 46.2%), followed by relapse (N = 18; 34.6%). Acute GvHD developed in 30 patients (31.3%), while chronic GvHD occurred in 25 patients (26.0%), resulting in a total of 45 patients (46.9%) experiencing GvHD. Male recipients with female donors had significantly worse overall survival compared to other patients (P = 0.01; HR = 2.33). Overall survival was better in patients transplanted within 1 year from the diagnosis compared to those transplanted after 1 year (P = 0.03; HR = 1.93). No factor reached statistical significance regarding the impact on acute GvHD, chronic GvHD, or overall GvHD.
We confirmed that sex mismatch, specifically in the case of a female donor and a male recipient, significantly negatively affects overall survival after alloHSCT. Additionally, overall survival is significantly shorter when the interval between the diagnosis and alloHSCT exceeds one year.
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