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- Machaczka, Maciej, et al.
(författare)
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Allogeneic hematopoietic stem cell transplant with reduced-intensity conditioning for chronic lymphocytic leukemia in Sweden: does donor T-cell engraftment 3 months after transplant predict survival?
- 2012
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Ingår i: Leukemia and Lymphoma. - : Informa Healthcare. - 1042-8194 .- 1029-2403. ; 53:9, s. 1699-1705
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Tidskriftsartikel (refereegranskat)abstract
- Thirty-eight adult patients with chronic lymphocytic leukemia (CLL) underwent reduced-intensity conditioning (RIC) allogeneic stem cell transplant (allo-SCT) in Sweden between 1999 and 2007. The cumulative incidences of acute graft-versus-host disease (GVHD) grades II-IV and chronic GVHD were 29% and 47%, respectively. Rates of non-relapse mortality, progression-free survival (PFS) and overall survival (OS) were 18%, 47% and 74% at 1 year, and 21%, 25% and 45% at 5 years, respectively. T-cell chimerism after transplant was measured in 31 out of 34 patients (91%) surviving beyond day + 100. Seventeen patients achieved andgt; 90% donor T-cell engraftment at 3 months after allo-SCT and, compared with the 12 patients with andlt;= 90% donor T-cell engraftment, they showed favorable PFS at 1 year (82% vs. 33%, p = 0.002) and better long-term PFS and OS (p = 0.002 and 0.046, respectively). Donor T-cell engraftment of andgt; 90% at 3 months after RIC allo-SCT for CLL seems to predict favorable short-term and long-term outcome.
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| 5. |
- Machaczka, Maciej, et al.
(författare)
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Allogeneic hematopoietic stem cell transplantation with reduced-intensity conditioning for chronic lymphocytic leukemia in Sweden : Does donor T-cell engraftment 3 months after transplantation predict survival?
- 2012
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Ingår i: Leukemia and Lymphoma. - London : Informa Healthcare. - 1042-8194 .- 1029-2403. ; 53:9, s. 1699-1705
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Tidskriftsartikel (refereegranskat)abstract
- Thirty-eight adult patients with chronic lymphocytic leukemia (CLL) underwent reduced-intensity conditioning (RIC) allogeneic stem cell transplantation (allo-SCT) in Sweden between 1999 and 2007. The cumulative incidences of acute GVHD grades II-IV and chronic GVHD were 29% and 48%, respectively. Rates of non-relapse mortality, progression-free survival (PFS) and overall survival (OS) were 18%, 47% and 74% at 1 year, and 21%, 25% and 45% at 5 years, respectively. T-cell chimerism after transplantation was measured in 31 out of 34 patients (91%) surviving beyond day +100. Seventeen patients achieved >90% donor T-cell engraftment at 3 months after allo-SCT and, compared with the 12 patients with ≤90% donor T-cell engraftment, they showed favorable PFS at 1 year (82% vs. 33%, P=0.002), and better long-term PFS and OS (P=0.002 and 0.05 respectively). Donor T-cell engraftment of >90% at 3 months after RIC allo-SCT for CLL seems to predict favorable short-term and long-term outcome.
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- Machaczka, Maciej, et al.
(författare)
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High incidence of chronic graft-versus-host disease after myeloablative allogeneic stem cell transplantation for chronic lymphocytic leukemia in Sweden : graft-versus-leukemia effect protects against relapse
- 2013
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Ingår i: Medical Oncology. - : Springer Science and Business Media LLC. - 1559-131X .- 1357-0560. ; 30:4, s. 762-762
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Tidskriftsartikel (refereegranskat)abstract
- Allogeneic hematopoietic stem cell transplantation (allo-SCT) is a potentially curative treatment option for eligible patients with chronic lymphocytic leukemia (CLL). However, it is known that cure of CLL is only possible if a graft-versus-leukemia effect is present. Between 1994 and 2007, 48 adults underwent allo-SCT for poor-risk CLL in Sweden. Of these, ten (21%) patients aged 24-53 years (median: 46 years) received myeloablative conditioning (MAC), based on TBI and cyclophosphamide. All MAC patients had refractory, poorly controlled CLL before allo-SCT (partial remission in 9/10 patients and progressive disease in one). The cumulative incidence of acute graft-versus-host disease (GVHD) grades II-IV was 30%. Nine patients developed chronic GVHD; extensive in four. Rates of nonrelapse mortality at 1, 3 and 10 years were 0, 10 and 20%, respectively. Two patients relapsed 36 and 53 months after transplantation. Six patients were still alive after a median follow-up time of 11.5 years (range 5.9-13.7). The probabilities of relapse-free and overall survival from 1, 3 and 5 years after transplantation were 100, 90 and 70%, and 100, 90 and 80%, respectively. Nevertheless, our analysis of long-term outcome after MAC allo-SCT for CLL suggests that younger patients with poorly controlled CLL may benefit from MAC allo-SCT.
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- Omar, Hamdy Hassan
(författare)
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Strategies for management of EBV and adenovirus infections after allogeneic stem cell transplantation
- 2010
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Viral infections are one of the challenges that can threaten successful allogeneic HSCT especially during the period of immune reconstitution resulting in a high mortality risk. Adenoviruses and EBV are important viruses during this period. Adenovirus infections can cause invasive adenovirus disease and EBV can cause post transplant lymphoproliferative disease (PTLD). Both are associated with significant morbidity and mortality if they are not discovered early and preemptive treatments are not given. IL-7 is a non-redundant cytokine that has important functions in T-cell survival, proliferation and memory formation. It is a growth factor for pre B-cells. It may have a role to improve T cell reconstitution early after HSCT. The aim of the thesis was to develop strategies to prevent severe viral complications after allogeneic HSCT. In the adenovirus part, we aimed to study the predictive value of adenoviremia for the development of adenovirus disease and to examine a surveillance strategy to control adenovirus disease. In the EBV-PTLD part, we aimed to see the effect of prospective monitoring of EBV load on PTLD control and to study the role of IL-7/IL-7R on PTLD development. We characterized in paper I adenovirus infections in a Swedish adult cohort after allogeneic HSCT. We found that incidence of adenoviremia was 4.9% in the studied population. CMV and EBV infections may occur to a large extent in patients with adenoviremia. Most patients with positive adenovirus PCR had sustained adenoviremia. Preemptive treatment with cidofovir might be a good treatment option to control adenoviremia. In study II we examined a surveillance strategy to control adenovirus infections. We found that only 5% of the patients had adenoviremia, no one developed adenovirus disease, or required antiviral treatment. This surveillance strategy could be applied to children and high risk adults. Most adult patients had adenovirus specific Tcell immune response in the first three months after allogeneic HSCT. A monitoring strategy of patients at a high risk of EBV-PTLD was applied. The effect of the strategy was compared with results of a historical control group in whom the strategy was not applied. We showed that 5.6% of high risk patients in the study group developed PTLD and 1.9% died from PTLD with the corresponding numbers in the control group being 9.4 and 5.7% for development of PTLD and death due to PTLD, respectively. Splenectomy was found to be a high risk factor in the study group. This monitoring strategy was able to face the high risk factors and can be applied safely. In study IV we found reduced responsiveness of IL-7 by the STAT5 phosphorylation assay in both CD4+ and CD8+ T-cells in PTLD patients. However, the reduced responsiveness of IL-7 was found only in CD8+ T-cells in the control group. IL-7R was found to be more expressed in PTLD patients than controls and was found to be expressed on other immune cells. This functional dysfunction in IL-7/IL-7R may help to identify and monitor patients at a high risk of EBV-PTLD. In conclusion, surveillance strategy to monitor high risk patients can help to reduce severe virological complications. Monitoring of IL-7 function might be a predictor of EBV-PTLD.
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