Tıp Fakültesi / Faculty of Medicine
Permanent URI for this collectionhttps://hdl.handle.net/11727/1403
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Item Haploidentical Versus Matched Sibling Donor Hematopoietic Stem Cell Transplantation for Adult Patients with Relapsed/Refractory Acute Lymphoblastic Leukemia: A Study from the Acute Leukemia Working Party of the European Society for Blood and Marrow Transplantation(2021) Nagler, Arnon; Labopin, Myriam; Pioltelli, Pietro; Arat, Mutlu; Yakoub-Agha, Ibrahim; Kulagin, Aleksandr D.; Angelucci, Emanuele; Ozdogu, Hakan; Risitano, Antonio; Ciceri, Fabio; Ozkurt, Zubeyde Nur; Sanz, Jaime; Brissot, Eolia; Peric, Zinaida; Giebel, Sebastian; Mohty, MohamadItem Haploidentical Versus Matched Sibling Donor Hematopoietic Stem Cell Transplantation for Adult Patients With Relapsed/Refractory Acute Lymphoblastic Leukemia: A Study From the Acute Leukemia Working Party of the European Society for Blood and Marrow Transplantation(2022) Nagler, Arnon; Labopin, Myriam; Swoboda, Ryszard; Pioltelli, Pietro; Arat, Mutlu; Yakoub-Agha, Ibrahim; Kulagin, Alexander; Maria Raiola, Anna; Ozdogu, Hakan; Risitano, Antonio; Nur Ozkurt, Zubeyde; Sanz, Jaime; Brissot, Eolia; Zina, Peric; Giebel, Sebastian; Ciceri, Fabio; Mohty, Mohamad; 000892089600008The results of haploidentical stem cell transplantation (haploHCT) for patients with acute lymphoblastic leukemia (ALL) transplanted in active disease remain largely unknown. We retrospectively analyzed adult patients with R/R ALL who underwent haploHCT or matched sibling donor (MSD-HCT) as a first transplantation between 2012 and 2020. The analysis comprised 274 patients, 94 had a haploHCT, and 180 had an MSD-HCT. The median follow-up was 32 months. The median age was 33 (range 18-76) and 37 (18-76) years in the haplo- and MSD-HCT groups, respectively. Post-transplant cyclophosphamide (PTCy) was used in 88% of haploHCT and in 4% of the MSD-HCT group. Graft-versus-host disease grade III-IV was higher in haploHCT than in the MSD-HCT group (18% versus 9%; P = 0.042). The 2-year chronic (c) graft-versus-host disease rates were 17% versus 33% (hazard ratio [HR] = 0.56; P = 0.14), respectively. By multivariate analysis, relapse incidence, and leukemia-free survival were not significatively different between the transplant groups, while nonrelapse mortality (NRM) was significantly higher (25% versus 18% at 2 years; HR = 2.03; P = 0.042) and overall survival (OS) lower (22% versus 38% at 2 years; HR = 1.72; P = 0.009) in the haploHCT group compared with the MSD-HCT group. We conclude that the 2-year OS of R/R ALL patients undergoing MSD transplants is significantly better than in haploHCT with a higher NRM in the latter.Item Improved Outcomes of Haploidentical Hematopoietic Cell Transplantation with Total Body Irradiation-Based Myeloablative Conditioning in Acute Lymphoblastic Leukemia(2021) Dholaria, Bhagirathbhai; Labopin, Myriam; Angelucci, Emanuele; Tischer, Johanna; Arat, Mutlu; Ciceri, Fabio; Guelbas, Zafer; Sica, Simona; Ozdogu, Hakan; Diez-Martin, Jose Luis; Koc, Yener; Pavlu, Jiri; Socie, Gerard; Giebel, Sebastian; Savani, Bipin N.; Nagler, Arnon; Mohty, Mohamad; 0000-0002-8902-1283; 33830029; AAD-5542-2021The optimal myeloablative conditioning (MAC) for patients undergoing haploidentical hematopoietic cell transplantation (haplo-HCT) is unknown. We studied the outcomes of total body irradiation (TBI)-based versus chemotherapy (CT)-based MAC regimens in patients with acute lymphoblastic leukemia (ALL). The study included 427 patients who underwent first haplo-HCT with post-transplantation cyclophosphamide (PTCy), following TBI-based (n = 188; 44%) or CT-based (n = 239; 56%) MAC. The median patient age was 32 years. Fludarabine-TBI (72%) and thiotepa-busulfan-fludarabine (65%) were the most frequently used TBI- and CT-based regimens, respectively. In the TBI and CT cohorts, 2-year leukemia-free survival (LFS) was 45% versus 37% (P = .05), overall survival (OS) was 51% versus 47% (P = .18), relapse incidence (RI) was 34% versus 32% (P = .44), and nonrelapse mortality (NRM) was 21% versus 31% (P < .01). In the multivariate analysis, TBI was associated with lower NRM (hazard ratio [HR], 0.53; 95% confidence interval [CI], 0.33 to 0.86; P = .01), better LFS (HR, 0.71; 95% CI, 0.52 to 0.98; P =.04), and increased risk for grade II-IV acute graft-versus-host disease (GVHD) (HR, 1.59; 95% CI, 1.08 to 2.34; P = .02) compared with CT-based MAC. The type of conditioning regimen did not impact RI, chronic GVHD, OS, or GVHD-free, relapse-free survival after adjusting for transplantation-related variables. TBI-based MAC was associated with lower NRM and better LFS compared with CT-based MAC in patients with ALL after haplo-HCT/PTCy. (C) 2020 The American Society for Transplantation and Cellular Therapy. Published by Elsevier Inc. All rights reserved.Item Post-transplant cyclophosphamide versus anti-thymocyte globulin for graft-versus-host disease prevention in haploidentical transplantation for adult acute lymphoblastic leukemia(2021) Nagler, Arnon; Kanate, Abraham S.; Labopin, Myriam; Ciceri, Fabio; Angelucci, Emanuele; Koc, Yener; Gulbas, Zafer; Arcese, William; Tischer, Johanna; Pioltelli, Pietro; Ozdogu, Hakan; Afanasyev, Boris; Wu, Depei; Arat, Mutlu; Peric, Zinaida; Giebel, Sebastian; Savani, Bipin; Mohty, Mohamad; 32354866Graft-versus-host disease (GvHD) prophylaxis for unmanipulated haploidentical hematopoietic cell transplantation includes posttransplant cyclophosphamide (PTCy) and anti-thymocyte globulin (ATG). Utilizing data in the European Society for Blood and Marrow Transplantation registry, we compared ATG- versus PTCy-based GvHD prophylaxis in 434 adults with acute lymphoblastic leukemia undergoing haploidentical hematopoietic cell transplantation. Of the 434 patients included in this study, ATG was used in 98 and PTCy in 336.. The median follow-up was approximately 2 years. The baseline characteristics of the patients were similar between the groups except that the ATG group was more likely to have had relapsed/refractory acute lymphoblastic leukemia (P=0.008), had conditioning not including total body irradiation (P<0.001), have had peripheral blood as the source of their grafts (P=0.001) and to have been transplanted in an earlier timeperiod (median year of transplantation: 2011 vs. 2015). The 100-day rates of grade II-IV and III-IV acute GvHD were similar in the ATG and PTCy groups, as were 2-year chronic GvHD rates. On multivariate analysis, leukemia-free survival and overall survival were better with PTCy than with ATG prophylaxis. Relapse incidence was lower in the PTCy group (P=0.03), while non-relapse mortality was not different. Advanced disease and lower performance score were associated with poorer leukemia-free survival and overall survival and advanced disease was associated with inferior GvHD-free/relapse-free survival. Compared to bone marrow grafts, peripheral grafts were associated with higher rates of GvHD. In patients with acute lymphoblastic leukemia undergoing unmanipulated haploidentical hematopoietic cell transplantation, PTCy for GvHD prevention resulted in a lower incidence of relapse and improved leukemia-free survival and overall survival, compared to ATG.Item Impact of in vivo T cell depletion in HLA-identical allogeneic stem cell transplantation for acute myeloid leukemia in first complete remission conditioned with a fludarabine iv-busulfan myeloablative regimen: a report from the EBMT Acute Leukemia Working Party(2017) Ozdogu, Hakan; Rubio, Marie Therese; D'Aveni-Piney, Maud; Labopin, Myriam; Hamladji, Rose-Marie; Sanz, Miguel A.; Blaise, Didier; Daguindeau, Etienne; Richard, Carlos; Santarone, Stella; Irrera, Giuseppe; Yakoub-Agha, Ibrahim; Yeshurun, Moshe; Diez-Martin, Jose L.; Mohty, Mohamad; Savani, Bipin N.; Nagler, Arnon; 0000-0002-8902-1283; 28118857; AAD-5542-2021Background: The impact of the use of anti-thymocyte globulin (ATG) in allogeneic stem cell transplantation performed with HLA-identical sibling donors following fludarabine and 4 days intravenous busulfan myeloablative conditioning regimen has been poorly explored. Methods: We retrospectively analyzed 566 patients who underwent a first HLA-identical allogeneic stem cell transplantation with this conditioning regimen for acute myeloid leukemia in first complete remission between 2006 and 2013 and compared the outcomes of 145 (25.6%) patients who received ATG (ATG group) to 421 (74.4%) who did not (no-ATG group). The Kaplan-Meier estimator, the cumulative incidence function, and Cox proportional hazards regression models were used where appropriate. Results: Patients in the ATG group were older, received more frequently peripheral blood stem cell grafts from older donors, and were transplanted more recently. With a median follow-up of 19 months, patients in the ATG group had reduced 2-year cumulative incidence of chronic graft-versus-host disease (GVHD) (31 vs. 52%, p = 0.0002) and of its extensive form (8 vs. 26%, p < 0.0001) but similar relapse incidence (22 vs. 27%, p = 0.23) leading to improved GVHD and relapse-free survival (GRFS) (60 vs. 40%, p = 0.0001). In multivariate analyses, the addition of ATG was independently associated with lower chronic GVHD (HR = 0.46, p = 0.0001), improved leukemia-free survival (HR = 0.67, p = 0.027), overall survival (HR = 0.65, p = 0.027), and GRFS (HR = 0.51, p=4 x 10(-5)). Recipient age above 50 years was the only other factor associated with worse survivals. Conclusions: These results suggest that the use of ATG with fludarabine and 4 days intravenous busulfan followed by HLA-identical sibling donor allogeneic stem cell transplantation for acute myeloid leukemia improves overall transplant outcomes due to reduced incidence of chronic GVHD without increased relapse risk.