Experimental and clinical transplantation : official journal of the Middle East Society for Organ Transplantation, Jan 11, 2021
Objectives: Our aim was to compare patients with high-risk chronic lymphocytic leukemia referred ... more Objectives: Our aim was to compare patients with high-risk chronic lymphocytic leukemia referred to our transplant center who underwent allogeneic stem cell transplant with those who did not receive this treatment. Factors compared included demographics, clinical characteristics, and survival rates in the novel targeted therapy era. Materials and methods: All 33 patients with high-risk chronic lymphocytic leukemia who were referred to the hematopoietic stem cell transplant center were enrolled in this retrospective, single-center nonrandomized study. Outcomes of patients who received allogeneic stem cell transplant were compared with those of nontransplant patients. Chemoimmunotherapy and ibrutinib were given when indicated. Factors related to overall and progression-free survival were assessed. Results: Thirteen patients underwent allotransplant, and transplant was not done in 20 patients for various reasons. Demographic and clinical features of the transplant and nontransplant groups were similar. The estimated cumulative overall survival was 72.6 ± 15 and 84.3 ± 13 months in the nontransplant and transplant groups, respectively. The 5-year overall and progression-free survival rates in the transplant and nontransplant groups were 57.3%/36.0% and 40%/20.6%, respectively. In the nontransplant group, overall survival of those who used ibrutinib was longer than overall survival in patients in the transplant group who used the same drug, but the difference was not statistically significant. Although not significant, overall survival in patients who did not use ibrutinib was longer in the transplant group than in the nontransplant group. Cox regression analyses showed that transplant, relapse, and Binet stage were independent predictors of overall survival. Conclusions: In patients who do not use ibrutinib, allogeneic stem cell transplant improved survival compared with nontransplant patients. Addition of ibrutinib provided comparable life expectancies, showing that allogeneic stem cell transplant and ibrutinib may have complementary roles. Transplant is still an independent predictor of overall survival.
BACKGROUNDGraft‐versus‐host disease (GVHD) is a major complication after allogeneic hematopoietic... more BACKGROUNDGraft‐versus‐host disease (GVHD) is a major complication after allogeneic hematopoietic stem cell transplantation (allo‐HSCT). Addition of antithymocyte globulin (ATG) or post‐transplantation cyclophosphamide (PTCY) to standard immunosuppressive agents reduces GVHD in different donor settings.METHODSWe compared the outcomes of adults with acute myeloid leukemia undergoing allo‐HSCT from HLA‐identical sibling donors after the use of PTCY (n = 197) or ATG (n = 1913).RESULTSPatients in the PTCY group were younger than those in the ATG group (median age, 47 vs 54 years; P < .01). Peripheral blood was the most frequently used stem cell source, being significantly more frequent in the ATG group than in the PTCY group (95% vs 70% P < .01). The conditioning regimen was more frequently myeloablative in the PTCY group than in the ATG group (59% vs 48%; P < .01). Time to neutrophil engraftment was shorter in the ATG group than in the PTCY group (17 vs 20 days; P < .01). No differences were observed according to the other transplantation outcomes, except for chronic GVHD of all grades and extensive chronic GVHD at 2 years, which were significantly lower in the ATG group compared with the PTCY group (P < .02).CONCLUSIONPTCY is feasible in an HLA‐identical sibling setting, and despite similar outcomes, ATG may be associated with lower incidence of chronic GVHD.
Survival after Allo-HSCT for severe idiopathic aplastic anemia (SAA) has improved in recent years... more Survival after Allo-HSCT for severe idiopathic aplastic anemia (SAA) has improved in recent years, approaching 75% at 5 years. However, an SAA-adapted composite endpoint, 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 SAAWP of the EBMT included 479 patients with idiopathic SAA who underwent Allo-HSCT in 2 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 (HR: 4.08, 9...
Paroxysmal nocturnal hemoglobinuria (PNH) is a rare X-linked genetic disorder. On the contrary to... more Paroxysmal nocturnal hemoglobinuria (PNH) is a rare X-linked genetic disorder. On the contrary to its name, it is a multisystemic disease and various symptoms other than hemoglobinuria could be occurred. It could be life threatening especially because of thromboembolic events. In the last decade, a terminal complement inhibition with eculizumab approved with promising results for PNH patients. We conducted this study to evaluate the long term experience of eculizumab therapy from Turkey for the first time. Our cohort included 138 patients with PNH treated with eculizumab between January 2008 and December 2018 at 28 centers in Turkey. Laboratory and clinical findings at the time of diagnosis and after eculizumab therapy were recorded retrospectively. The median age was 39 (range 18-84) years and median granulocyte PNH clone size was 74% (range 3.06-99.84%) at the time of diagnosis. PNH with bone marrow failure syndrome was detected in 49 patients and the rest of 89 patients had class...
WOS: 000445782800016TUBITAKTurkiye Bilimsel ve Teknolojik Arastirma Kurumu (TUBITAK) [111S391]Thi... more WOS: 000445782800016TUBITAKTurkiye Bilimsel ve Teknolojik Arastirma Kurumu (TUBITAK) [111S391]This study was supported by TUBITAK with the Project number 111S391 to Y.B
Background: Treosulfan has been increasingly used in reduced toxicity regimens, especially in old... more Background: Treosulfan has been increasingly used in reduced toxicity regimens, especially in older or frail patients. Different doses of treosulfan plus fludarabine have shown an advantage over reduced intensity regimens, confirmed by a randomized phase 3 trial utilizing treosulfan 30 g/m² (or FT10) in the majority of patients. However, data comparing fludarabine with higher doses of treosulfan (FT14) to fludarabine combined with myeloablative doses of busulfan are limited. Aims: We compared outcomes between treatment alternatives of similar conditioning intensity: FT14 (fludarabine 150 or 160 mg/m 2 and treosulfan 42g/m 2, or FT14) over FB4 (fludarabine 150 or 160 mg/m 2 and busulfan 12.8 mg/kg). Methods: We retrospectively studied consecutive patients from the European Society for Blood and Marrow Transplantation (EBMT) registry, meeting the following inclusion criteria: a) adults diagnosed with acute myeloid leukemia (AML), b) recipients of first allogeneic hematopoietic stem ce...
Background: Outcomes of Haploidentical transplantation (HaploSCT) in adult patients (pts) with ac... more Background: Outcomes of Haploidentical transplantation (HaploSCT) in adult patients (pts) with acute relapsed/refractory lymphoblastic leukemia (Rel/Ref ALL) are comparable to unrelated donor transplants. We have recently reported that results of HaploSCT for ALL in remission are not significantly different from those receiving transplants from matched sibling donors (MSD). However, results may differ in ALL pts with active disease. Aim: To compare outcomes of HaploSCT and MSD transplantations in pts with Rel/Ref ALL. Methods: We retrospectively analyzed adult patients (≥ 18 years) with Rel/Ref ALL who underwent their first transplantation between 2012 and 2020, either from a T cell replete Haplo or MSD donor. Multivariate analysis (MVA) adjusting for differences between the groups was performed using the Cox proportional- hazards regression model. Results: The analysis comprised 274 pts: HaploSCT-94 (34%); MSD-180 (66%). Median follow-up was 32 months. Median age was 33 (range 18-7...
The optimal myeloablative conditioning (MAC) for patients undergoing haploidentical hematopoietic... more The 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.
Experimental and clinical transplantation : official journal of the Middle East Society for Organ Transplantation, Jan 11, 2021
Objectives: Our aim was to compare patients with high-risk chronic lymphocytic leukemia referred ... more Objectives: Our aim was to compare patients with high-risk chronic lymphocytic leukemia referred to our transplant center who underwent allogeneic stem cell transplant with those who did not receive this treatment. Factors compared included demographics, clinical characteristics, and survival rates in the novel targeted therapy era. Materials and methods: All 33 patients with high-risk chronic lymphocytic leukemia who were referred to the hematopoietic stem cell transplant center were enrolled in this retrospective, single-center nonrandomized study. Outcomes of patients who received allogeneic stem cell transplant were compared with those of nontransplant patients. Chemoimmunotherapy and ibrutinib were given when indicated. Factors related to overall and progression-free survival were assessed. Results: Thirteen patients underwent allotransplant, and transplant was not done in 20 patients for various reasons. Demographic and clinical features of the transplant and nontransplant groups were similar. The estimated cumulative overall survival was 72.6 ± 15 and 84.3 ± 13 months in the nontransplant and transplant groups, respectively. The 5-year overall and progression-free survival rates in the transplant and nontransplant groups were 57.3%/36.0% and 40%/20.6%, respectively. In the nontransplant group, overall survival of those who used ibrutinib was longer than overall survival in patients in the transplant group who used the same drug, but the difference was not statistically significant. Although not significant, overall survival in patients who did not use ibrutinib was longer in the transplant group than in the nontransplant group. Cox regression analyses showed that transplant, relapse, and Binet stage were independent predictors of overall survival. Conclusions: In patients who do not use ibrutinib, allogeneic stem cell transplant improved survival compared with nontransplant patients. Addition of ibrutinib provided comparable life expectancies, showing that allogeneic stem cell transplant and ibrutinib may have complementary roles. Transplant is still an independent predictor of overall survival.
BACKGROUNDGraft‐versus‐host disease (GVHD) is a major complication after allogeneic hematopoietic... more BACKGROUNDGraft‐versus‐host disease (GVHD) is a major complication after allogeneic hematopoietic stem cell transplantation (allo‐HSCT). Addition of antithymocyte globulin (ATG) or post‐transplantation cyclophosphamide (PTCY) to standard immunosuppressive agents reduces GVHD in different donor settings.METHODSWe compared the outcomes of adults with acute myeloid leukemia undergoing allo‐HSCT from HLA‐identical sibling donors after the use of PTCY (n = 197) or ATG (n = 1913).RESULTSPatients in the PTCY group were younger than those in the ATG group (median age, 47 vs 54 years; P &lt; .01). Peripheral blood was the most frequently used stem cell source, being significantly more frequent in the ATG group than in the PTCY group (95% vs 70% P &lt; .01). The conditioning regimen was more frequently myeloablative in the PTCY group than in the ATG group (59% vs 48%; P &lt; .01). Time to neutrophil engraftment was shorter in the ATG group than in the PTCY group (17 vs 20 days; P &lt; .01). No differences were observed according to the other transplantation outcomes, except for chronic GVHD of all grades and extensive chronic GVHD at 2 years, which were significantly lower in the ATG group compared with the PTCY group (P &lt; .02).CONCLUSIONPTCY is feasible in an HLA‐identical sibling setting, and despite similar outcomes, ATG may be associated with lower incidence of chronic GVHD.
Survival after Allo-HSCT for severe idiopathic aplastic anemia (SAA) has improved in recent years... more Survival after Allo-HSCT for severe idiopathic aplastic anemia (SAA) has improved in recent years, approaching 75% at 5 years. However, an SAA-adapted composite endpoint, 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 SAAWP of the EBMT included 479 patients with idiopathic SAA who underwent Allo-HSCT in 2 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 (HR: 4.08, 9...
Paroxysmal nocturnal hemoglobinuria (PNH) is a rare X-linked genetic disorder. On the contrary to... more Paroxysmal nocturnal hemoglobinuria (PNH) is a rare X-linked genetic disorder. On the contrary to its name, it is a multisystemic disease and various symptoms other than hemoglobinuria could be occurred. It could be life threatening especially because of thromboembolic events. In the last decade, a terminal complement inhibition with eculizumab approved with promising results for PNH patients. We conducted this study to evaluate the long term experience of eculizumab therapy from Turkey for the first time. Our cohort included 138 patients with PNH treated with eculizumab between January 2008 and December 2018 at 28 centers in Turkey. Laboratory and clinical findings at the time of diagnosis and after eculizumab therapy were recorded retrospectively. The median age was 39 (range 18-84) years and median granulocyte PNH clone size was 74% (range 3.06-99.84%) at the time of diagnosis. PNH with bone marrow failure syndrome was detected in 49 patients and the rest of 89 patients had class...
WOS: 000445782800016TUBITAKTurkiye Bilimsel ve Teknolojik Arastirma Kurumu (TUBITAK) [111S391]Thi... more WOS: 000445782800016TUBITAKTurkiye Bilimsel ve Teknolojik Arastirma Kurumu (TUBITAK) [111S391]This study was supported by TUBITAK with the Project number 111S391 to Y.B
Background: Treosulfan has been increasingly used in reduced toxicity regimens, especially in old... more Background: Treosulfan has been increasingly used in reduced toxicity regimens, especially in older or frail patients. Different doses of treosulfan plus fludarabine have shown an advantage over reduced intensity regimens, confirmed by a randomized phase 3 trial utilizing treosulfan 30 g/m² (or FT10) in the majority of patients. However, data comparing fludarabine with higher doses of treosulfan (FT14) to fludarabine combined with myeloablative doses of busulfan are limited. Aims: We compared outcomes between treatment alternatives of similar conditioning intensity: FT14 (fludarabine 150 or 160 mg/m 2 and treosulfan 42g/m 2, or FT14) over FB4 (fludarabine 150 or 160 mg/m 2 and busulfan 12.8 mg/kg). Methods: We retrospectively studied consecutive patients from the European Society for Blood and Marrow Transplantation (EBMT) registry, meeting the following inclusion criteria: a) adults diagnosed with acute myeloid leukemia (AML), b) recipients of first allogeneic hematopoietic stem ce...
Background: Outcomes of Haploidentical transplantation (HaploSCT) in adult patients (pts) with ac... more Background: Outcomes of Haploidentical transplantation (HaploSCT) in adult patients (pts) with acute relapsed/refractory lymphoblastic leukemia (Rel/Ref ALL) are comparable to unrelated donor transplants. We have recently reported that results of HaploSCT for ALL in remission are not significantly different from those receiving transplants from matched sibling donors (MSD). However, results may differ in ALL pts with active disease. Aim: To compare outcomes of HaploSCT and MSD transplantations in pts with Rel/Ref ALL. Methods: We retrospectively analyzed adult patients (≥ 18 years) with Rel/Ref ALL who underwent their first transplantation between 2012 and 2020, either from a T cell replete Haplo or MSD donor. Multivariate analysis (MVA) adjusting for differences between the groups was performed using the Cox proportional- hazards regression model. Results: The analysis comprised 274 pts: HaploSCT-94 (34%); MSD-180 (66%). Median follow-up was 32 months. Median age was 33 (range 18-7...
The optimal myeloablative conditioning (MAC) for patients undergoing haploidentical hematopoietic... more The 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.
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