| 1. |
- Afram, Gabriel
(författare)
-
Clinical aspects of chronic graft-versus-host disease
- 2019
-
Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Chronic graft-versus-host disease (cGVHD) remains one of the most severe complications after allogeneic hematopoietic stem cell transplantation (HSCT), affecting both the quality of life and mortality of long-term survivors. Its impact on morbidity and mortality varies depending on the severity and number of organs involved, allowing classification into mild, moderate, and severe cGVHD according to the National Institute of Health criteria (NIH). Chronic GVHD is associated with a graft-versus-tumor effect (GVT) that decreases the risk of relapse after transplantation. Treatments involve potent immunosuppressive modalities with side effects including infections and possibly relapse of the underlying malignancy. The aim of this thesis is to increase the knowledge of cGVHD with emphasis on early detection of risk and prognostic factors in order to allow a more vigilant management of the syndrome as well as the evaluation of extracorporeal photopheresis. In paper I we performed a retrospective study with emphasis on risk factors for the development of cGVHD. We showed a significantly higher incidence of severe cGVHD in patients with sibling donors compared to unrelated donors (URD). Relapse and Transplant-related-mortality (TRM) were similar in both groups. However, TRM was significantly higher in patients with severe cGVHD. The main findings were that despite HSCTs with sibling donors showing higher incidence of cGVHD they resulted in significantly better 5-year overall survival (OS) and relapse-free survival (RFS) compared to patients with a URD. Paper II is a multi-centre retrospective analysis with the aim to determine early detectable risk factors for the development of cGVHD. We found that risk factors for severe cGVHD include female donor to male recipient, reduced intensity conditioning and older patient age. In 2005 the NIH formed consensus criteria for the diagnosis of cGVHD. The new scoring system proved time-consuming and difficult to manage during a standard out-patient visit. In paper III we aimed to determine the prognostic impact of the new NIH score and also of the newly implemented sub-categories of cGVHD, namely overlap syndrome and delayed acute GVHD. Our aim was to develop a simplified score with similar prognostic impact as that of the NIH score. We could show that factors adversely affecting prognosis upon diagnosis of cGVHD include ECOG, platelet count and, if present, severe gut involvement. In fact, by only using the combination of ECOG and platelet count we could identify the same prognostic risk groups. The most well-established second line treatment for steroid-refractory, - intolerant or –dependent cGVHD to date is extracorporeal photopheresis (ECP). In paper IV we could conclude that ECP was a safe and well-tolerated treatment. Patients with severe skin cGVHD had the best response in terms of complete or partial response. To summarize, this thesis provides new data regarding risk and prognostic factors for cGVHD which has led to perhaps a more-user friendly prognostic tool upon diagnosis of cGVHD. The findings help us to decide on immunosuppression for URD and what patient group would benefit the most from ECP treatment.
|
|
| 2. |
- Afram, Gabriel, et al.
(författare)
-
Higher response rates in patients with severe chronic skin graft-versus-host disease treated with extracorporeal photopheresis
- 2019
-
Ingår i: Central European Journal of Immunology. - : TERMEDIA PUBLISHING HOUSE LTD. - 1426-3912 .- 1644-4124. ; 44:1, s. 84-91
-
Tidskriftsartikel (refereegranskat)abstract
- Introduction: Different forms of graft-versus-host disease (GVHD) remain a major cause of morbidity and mortality after allogeneic hematopoietic stem cell transplantation (HSCT). The prognosis for steroid-refractory chronic GVHD (cGVHD) remains poor. Our aim was to evaluate extracorporeal photopheresis (ECP) treatment in cGVHD patients with different organ involvement to detect subgroups of patients with the best response.Material and methods: Thirty-four patients who underwent HSCT and developed moderate (n = 7) or severe (n = 27) steroid-refractory or steroid-dependent cGVHD treated with ECP were included in the analysis. A matched cGVHD control patient group untreated with ECP was collected for comparison.Results: Compared to the control group and the stable/progressive disease (SD/PD) patients, individuals with complete/partial remission have higher overall survival and lower transplant-related mortality. Furthermore, patients with complete and partial remission (CR/PR) had significantly higher levels of albumin and platelets after ECP treatment compared to patients with stable or progressive cGVHD (SD/PD). Corticosteroid treatment and other immunosuppressive agents could successfully be tapered in the CR/PR group compared to the SD/PD patients. In this study patients with skin cGVHD are those with the highest rate of CR/PR after ECP treatment.Conclusions: Our results suggest that ECP treatment is safe and effective for patients with predominantly skin, oral and liver cGVHD.
|
|
| 3. |
- Afram, Gabriel, et al.
(författare)
-
Reduced intensity conditioning increases risk of severe cGVHD : identification of risk factors for cGVHD in a multicenter setting
- 2018
-
Ingår i: Medical Oncology. - : Springer Science and Business Media LLC. - 1357-0560 .- 1559-131X. ; 35:6
-
Tidskriftsartikel (refereegranskat)abstract
- Chronic graft-versus-host disease (cGVHD) remains a major cause of morbidity and mortality after allogeneic hematopoietic stem cell transplantation (HSCT). Aim is to identify risk factors for the development of cGVHD in a multicenter setting. Patients transplanted between 2000 and 2006 were analyzed (n = 820). Donors were HLA-identical siblings (57%), matched unrelated donors (30%), and HLA-A, B or DR antigen mismatched (13%). Reduced intensity conditioning (RIC) was given to 65% of patients. Overall incidence of cGVHD was 46% for patients surviving more than 100 days after HSCT (n = 747). Older patient age [HR 1.15, p < 0.001], prior acute GVHD [1.30, p = 0.024], and RIC [1.36, p = 0.028] increased overall cGVHD. In addition, RIC [4.85, p < 0.001], prior aGVHD [2.14, p = 0.001] and female donor to male recipient [1.80, p = 0.008] increased the risk of severe cGVHD. ATG had a protective effect for both overall [0.41, p < 0.001] and severe cGVHD [0.20, p < 0.001]. Relapse-free survival (RFS) was impaired in patients with severe cGVHD. RIC, prior aGVHD, and female-to-male donation increase the risk of severe cGVHD. ATG reduces the risk of all grades of cGVHD without hampering RFS. GVHD prophylaxis may be tailored according to the risk profile of patients.
|
|
| 4. |
- Nahi, Hareth, et al.
(författare)
-
Minimal residual disease status is the prognostic determinant following high-dose treatment for patients with multiple myeloma
- 2023
-
Ingår i: Cancer Medicine. - : WILEY. - 2045-7634. ; 12:22, s. 20736-20744
-
Tidskriftsartikel (refereegranskat)abstract
- Background: The presence of minimal residual disease (MRD+) following autologous stem cell transplantation (ASCT) in multiple myeloma represents a poor prognostic factor for progression-free survival (PFS) and overall survival (OS).Methods: At our department, we recommend lenalidomide maintenance for patients who are MRD+ after ASCT, while MRD-negative (MRD-) patients, after information about the national guidelines, were not advised to follow this regimen.Results: Out of the total 228 patients, 175 received ASCT following first-line induction (MRD- 92 (53%), MRD+ 83 (47%), at 2 months post-ASCT), while 53 underwent ASCT after second-line treatment (MRD- 27 (51%), MRD+ 26 (49%), at the same time point). Comparatively, MRD- patients who did not receive maintenance demonstrated better OS than MRD+ patients who received upfront ASCT and maintenance treatment (96% vs. 86%, p = 0.030, at 3 years). However, nonsignificant difference was found in PFS (76% vs. 62%, at 3 years). Furthermore, second-line ASCT, MRD- non-maintained patients exhibited significantly better PFS than MRD+ (71% vs. 27%, p > 0.001, at 3 years). However, OS was better but nonsignificant (96% vs. 76%, at 3 years). Fluorescence in situ hybridization (FISH) analysis was performed on 141 out of the 228 patients. Of these, 85 (60%) patients were deemed standard risk (SR), and 56 (40%) were classified as high risk (HR). In the SR cohort, MRD- patients exhibited better PFS and OS than MRD+ patients (71% vs. 59% and 100% vs. 85%, respectively). In the HR cohort, the MRD- patients showed superior PFS but similar OS compared to MRD+ patients (66% vs. 42% and 81% vs. 80%, respectively).Conclusions: Our results indicate that being MRD- is a more crucial prognostic factor for the 3-year PFS and OS than the presence of high-risk cytogenetic markers or undergoing maintenance treatment. The latter appears insufficient, particularly for MRD+ patients following ASCT in the second-line setting, suggesting that these patients may require a more intensive treatment approach.
|
|
| 5. |
- Pérez-Simón, Jose A, et al.
(författare)
-
Evaluation of prognostic factors among patients with chronic graft-versus-host disease
- 2012
-
Ingår i: Haematologica. - : Ferrata Storti Foundation (Haematologica). - 0390-6078 .- 1592-8721. ; 97:8, s. 1187-1195
-
Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND:Chronic graft-versus-host disease (cGVHD) is a major complication after allogeneic stem cell transplantation with an adverse effect on both mortality and morbidity. In 2005, the National Institute of Health proposed new criteria for diagnosis and classification of chronic graft-versus-host disease for clinical trials. New sub-categories were recognized such as late onset acute graft-versus-host disease and overlap syndrome.DESIGN AND METHODS:We evaluated the prognostic impact of the new sub-categories as well as the clinical scoring system proposed by the National Institute of Health in a retrospective, multicenter study of 820 patients undergoing allogeneic stem cell transplantation between 2000 and 2006 at 3 different institutions. Patients were retrospectively categorized according to the National Institute of Health criteria from patients' medical histories.RESULTS:As far as the new sub-categories are concerned, in univariate analysis diagnosis of overlap syndrome adversely affected the outcome. Also, the number of organs involved for a cut-off value of 4 significantly influenced both cGVHD related mortality and survival. In multivariate analysis, in addition to NIH score, platelet count and performance score at the time of cGVHD diagnosis, plus gut involvement, significantly influenced outcome. These 3 variables allowed us to develop a simple score system which identifies 4 subgroups of patients with 84%, 64%, 43% and 0% overall survival at five years after cGVHD diagnosis (score 0: HR=15.96 (95% CI: 6.85-37.17), P<0.001; score 1: HR=5.47 (95% CI: 2.6-11.5), P<0.001; score 2: HR=2.8 (95% CI: 1.32-5.93), P=0.007).CONCLUSIONS:In summary, we have identified a powerful and simple tool to discriminate different subgroups of patients in terms of chronic graft-versus-host disease related mortality and survival.
|
|
