Tıp Fakültesi / Faculty of Medicine
Permanent URI for this collectionhttps://hdl.handle.net/11727/1403
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Item Graft-Versus-Host Disease and Relapse/Rejection-Free Survival After Allogeneic Transplantation for Idiopathic Severe Aplastic Anemia: A Comprehensive Analysis from the SAAWP of the EBMT(2023) Devillier, Raynier; Eikema, Dirk-Jan; Dufour, Carlo; Aljurf, Mahmoud; Wu, Depei; Maschan, Alexei; Kulagin, Alexander; Halkes, Constantijn J. M.; Collin, Matthew; Snowden, John; Renard, Cecile; Ganser, Arnold; Sykora, Karl-Walter; Gibson, Brenda E.; Maertens, Johan; Itala-Remes, Maija; Corti, Paola; Cornelissen, Jan; Bornhaeuser, Martin; Colorado Araujo, Mercedes; Ozdogu, Hakan; Risitano, Antonio; Socie, Gerard; de latour, Regis Peffault; 36951165Survival after allogeneic hematopoietic stem cell transplantation (allo-HSCT) for severe idiopathic aplastic anemia (SAA) has improved in recent years, approaching 75% at 5 years. However, an SAA-adapted composite endpoint, graft-versus-host disease (GvHD) and relapse/rejection-free survival (GRFS), may more accurately assess patient outcomes beyond survival. We analyzed GRFS to identify risk factors and specific causes of GRFS failure. Our retrospective analysis from the Severe Aplastic Anemia Working Party of the European Society for Blood and Marrow Transplantation included 479 patients with idiopathic SAA who underwent allo-HSCT in two conventional situations: i) upfront allo-HSCT from a matched related donor (MRD) (upfront cohort), and ii) allo-HSCT for relapsed or refractory SAA (rel/ref cohort). Relevant events for GRFS calculation included graft failure, grade 3-4 acute GvHD, extensive chronic GvHD, and death. In the upfront cohort (n=209), 5-year GRFS was 77%. Late allo-HSCT (i.e., >6 months after SAA diagnosis) was the main poor prognostic factor, specifically increasing the risk of death as the cause of GRFS failure (hazard ratio [HR]=4.08; 95% confidence interval [CI]: 1.41-11.83; P=0.010). In the rel/ref cohort (n=270), 5-year GRFS was 61%. Age was the main factor significantly increasing the risk of death (HR=1.04; 95% CI: 1.02-1.06; P<0.001), acute GvHD (HR=1.03; 95% CI: 1.00-1.07; P=0.041), and chronic GvHD (HR=1.04; 95% CI: 1.01-1.08; P=0.032) as the cause of GRFS failure. GRFS after upfront MRD allo-HSCT was very good, notably with early allo-HSCT, confirming that younger patients with an MRD should be transplanted immediately. GRFS was worse in cases of salvage allo-HSCT, most notably in older patients, questioning the utility of allo-HSCT earlier in the disease course.Item Total Body Irradiation Plus Fludarabine Versus Busulfan Plus Fludarabine As A Myeloablative Conditioning for Adults with Acute Myeloid Leukemia Treated with Allogeneic Hematopoietic Cell Transplantation. A Study on Behalf of The Acute Leukemia Working Party of The EBMT(2022) Swoboda, Ryszard; Labopin, Myriam; Giebel, Sebastian; Schroeder, Thomas; Kroeger, Nicolaus; Arat, Mutlu; Savani, Bipin; Spyridonidis, Alexandros; Hamladji, Rose-Marie; Potter, Victoria; Berceanu, Ana; Yakoub-Agha, Ibrahim; Rambaldi, Alessandro; Ozdogu, Hakan; Sanz, Jaime; Nagler, Arnon; Mohty, Mohamad; 36460819Cyclophosphamide is frequently substituted with fludarabine (Flu) in conditioning regimens before allogeneic hematopoietic cell transplantation (allo-HCT). We aimed to compare retrospectively, total body irradiation (12 Gy) plus Flu (FluTBI12) versus busulfan (Bu) plus Flu (FB4) as a myeloablative conditioning before allo-HCT in patients with acute myeloid leukemia (AML). Out of 3203 patients who met the inclusion criteria, 109 patients treated with FluTBI12 and 213 treated with FB4 were included in a final matched-pair analysis. In both groups, median patient age was 41 years, first or second complete remission (CR1/CR2) proportion was 78%/22%, allo-HCT from an unrelated donor was performed in 78% of patients. The probabilities of leukemia-free survival and overall survival at 2 years in FluTBI12 and FB4 groups were 65% vs. 60% (p = 0.64) and 70% vs. 72% (p = 0.87), respectively. The cumulative incidence of relapse was 19% vs. 29% (p = 0.11), while non-relapse mortality was 16% vs. 11%, respectively (p = 0.13). There were no statistical differences in both acute and chronic graft-versus-host disease (GVHD) incidence. The probability of GVHD-free, relapse-free survival (GRFS) was 49% for both groups. FluTBI12 and FB4 are comparable myeloablative regimens before allo-HCT in AML patients transplanted in CR1 and CR2.Item Incidence and outcome of Kaposi sarcoma after hematopoietic stem cell transplantation: a retrospective analysis and a review of the literature, on behalf of infectious diseases working party of EBMT(2020) Cesaro, Simone; Tridello, Gloria; van der Werf, Steffie; Bader, Peter; Socie, Gerard; Ljungman, Per; McQuaker, Grant; Giardino, Stefano; ckan-Cetinkaya, Duygu; Anagnostopoulos, Achilles; Ozdogu, Hakan; Schots, Rik; Jindra, Pavel; Ladetto, Marco; Schroyens, Wilfried; Mikulska, Malgorzata; Styczynski, Jan; 0000-0002-8902-1283; 31435035; AAD-5542-2021The incidence, the clinical characteristics, and the outcome of Kaposi sarcoma (KS) in patients after hematopoietic stem cell transplantation (HSCT) were assessed. During the period 1987-2018, 13 cases of KS were diagnosed, 3 females and 10 males, median age of 50 years, median time from HSCT of 7 months. KS had an incidence of 0.17% in allogeneic and 0.05% in autologous HSCT. HHV-8 was documented in eight of nine tumor tissue samples assessed. The organ involvement was: skin in nine, lymph nodes in six, oral cavity in four, and visceral in three patients, respectively; seven patients had >1 organ involved. Five patients had immunosuppression withdrawn, whereas four and three patients received radiotherapy and chemotherapy, respectively. Eight patients are alive (median follow-up 48 months, range 5-128), whereas five patients died after a median time of 8 months from the diagnosis of KS. However, no death was caused by KS. We conclude that the incidence of KS after HSCT is very low. Although KS can be managed with the reduction of immunosuppression, visceral forms may require chemotherapy and/or radiotherapy. The low prevalence of KS indicates that screening for HHV-8 serology and surveillance for HHV-8 viremia are not indicated in HSCT patients.Item Total body irradiation plus fludarabine compared to busulfan plus fludarabine as "reduced-toxicity conditioning" for patients with acute myeloid leukemia treated with allogeneic hematopoietic cell transplantation in first complete remission: a study by the Acute Leukemia Working Party of the EBMT(2020) Ozdogu, Hakan; 0000-0002-8902-1283; 32892216; AAD-5542-2021The optimal conditioning for patients with acute myeloid leukemia in first complete remission treated with allogeneic hematopoietic cell transplantation (allo-HCT) has not been defined so far. In this retrospective study, we compared two "reduced-toxicity" regimens: intravenous busulfan at a total dose of 9.6 mg/kg (3 days) + fludarabine (Bu3/Flu) and total body irradiation at a dose of 8 Gy + fludarabine (TBI8Gy/Flu). In the entire study cohort (n = 518), the probabilities of overall survival (OS), leukemia-free survival (LFS), relapse and non-relapse mortality (NRM) at 2 years for Bu3/Flu and TBI8Gy/Flu were 62% vs. 72.5% (p = 0.051), 59.5% vs. 65% (p = 0.15), 30% vs. 20% (p = 0.01), and 10% vs. 14% (p = 0.18), respectively. In multivariate model for patients <50 years old, TBI8Gy/Flu was associated with improved LFS (hazard ratio (HR) = 0.5,p = 0.04), OS (HR = 0.31,p = 0.004), and survival free from both graft-versus-host disease and relapse (HR = 0.55,p = 0.03), as well as tendency to reduced risk of relapse (HR = 0.53,p = 0.08). Among patients aged 50 years or older the use of TBI8Gy/Flu was associated with increased incidence of NRM (HR = 3.9,p = 0.0009), with no significant impact on other outcome measures. We conclude that the use of TBI8Gy/Flu as "reduced-toxicity" regimen may be advised in younger patients with AML referred for allo-HCT