| 1. |
- Ahmed, Sairah, et al.
(författare)
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Impact of type of reduced-intensity conditioning regimen on the outcomes of allogeneic haematopoietic cell transplantation in classical Hodgkin lymphoma
- 2020
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Ingår i: British Journal of Haematology. - : WILEY. - 0007-1048 .- 1365-2141. ; 190:4, s. 573-582
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Tidskriftsartikel (refereegranskat)abstract
- Reduced-intensity conditioning (RIC) allogeneic haematopoietic cell transplantation (allo-HCT) is a curative option for select relapsed/refractory Hodgkin lymphoma (HL) patients; however, there are sparse data to support superiority of any particular conditioning regimen. We analyzed 492 adult patients undergoing human leucocyte antigen (HLA)-matched sibling or unrelated donor allo-HCT for HL between 2008 and 2016, utilizing RIC with either fludarabine/busulfan (Flu/Bu), fludarabine/melphalan (Flu/Mel140) or fludarabine/cyclophosphamide (Flu/Cy). Multivariable regression analysis was performed using a significance level of <0 center dot 01. There were no significant differences between regimens in risk for non-relapse mortality (NRM) (P = 0 center dot 54), relapse/progression (P = 0 center dot 02) or progression-free survival (PFS) (P = 0 center dot 14). Flu/Cy conditioning was associated with decreased risk of mortality in the first 11 months after allo-HCT (HR = 0 center dot 28; 95% CI = 0 center dot 10-0 center dot 73; P = 0 center dot 009), but beyond 11 months post allo-HCT it was associated with a significantly higher risk of mortality, (HR = 2 center dot 46; 95% CI = 0 center dot 1.32-4 center dot 61; P = 0 center dot 005). Four-year adjusted overall survival (OS) was similar across regimens at 62% for Flu/Bu, 59% for Flu/Mel140 and 55% for Flu/Cy (P = 0 center dot 64), respectively. These data confirm the choice of RIC for allo-HCT in HL does not influence risk of relapse, NRM or PFS. Although no OS benefit was seen between Flu/Bu and Flu/Mel 140; Flu/Cy was associated with a significantly higher risk of mortality beyond 11 months from allo-HCT (possibly due to late NRM events).
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| 2. |
- Jagadeesh, Deepa, et al.
(författare)
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Outcomes of rituximab‐BEAM versus BEAM conditioning regimen in patients with diffuse large B cell lymphoma undergoing autologous transplantation
- 2020
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Ingår i: Cancer. - : WILEY. - 0008-543X .- 1097-0142. ; 126:10, s. 2279-2287
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND Although rituximab-based high-dose therapy is frequently used in diffuse large B cell lymphoma (DLBCL) patients undergoing autologous hematopoietic cell transplantation (auto-HCT), data supporting the benefits are not available. Herein, we report the impact of rituximab-based conditioning on auto-HCT outcomes in patients who have DLBCL. METHODS Using the Center for International Blood and Marrow Transplant Research (CIBMTR) registry, 862 adult DLBCL patients undergoing auto-HCT between 2003 and 2017 using BEAM (BCNU, etoposide, cytarabine, melphalan) conditioning regimen were included. All patients received frontline rituximab-containing chemoimmunotherapy and had chemosensitive disease pre-HCT. Early chemoimmunotherapy failure was defined as not achieving complete remission (CR) after frontline chemoimmunotherapy or relapse within 1 year of initial diagnosis. The primary outcome was overall survival (OS). RESULTS The study cohort was divided into 2 groups: BEAM (n = 667) and R-BEAM (n = 195). On multivariate analysis, no significant difference was seen in OS (P = .83) or progression-free survival (PFS) (P = .61) across the 2 cohorts. No significant association between the use of rituximab and risk of relapse (P = .15) or nonrelapse mortality (P = .12) was observed. Variables independently associated with lower OS included older age at auto-HCT (P < .001), absence of CR at auto-HCT (P < .001) and early chemoimmunotherapy failure (P < .001). Older age (P < .0002) and non-CR pre-HCT (P < .0001) were also associated with inferior PFS. There was no significant difference in early infectious complications between the 2 cohorts. CONCLUSION In this large registry analysis of DLBCL patients undergoing auto-HCT, the addition of rituximab to the BEAM conditioning regimen had no impact on transplantation outcomes. Older age, absence of CR pre auto-HCT, and early chemoimmunotherapy failure were associated with inferior survival.
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| 3. |
- Jimenez, Antonio M. Jimenez, et al.
(författare)
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An adapted European LeukemiaNet genetic risk stratification for acute myeloid leukemia patients undergoing allogeneic hematopoietic cell transplant. A CIBMTR analysis
- 2021
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Ingår i: Bone Marrow Transplantation. - : Springer Nature. - 0268-3369 .- 1476-5365. ; 56:12, s. 3068-3077
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Tidskriftsartikel (refereegranskat)abstract
- Cytogenetic and molecular abnormalities are known to influence post-transplant outcomes in acute myeloid leukemia (AML) but data assessing the prognostic value of combined genetic models in the HCT setting are limited. We developed an adapted European LeukemiaNet (aELN) risk classification based on available genetic data reported to the Center for International Blood and Marrow Transplant Research, to predict post-transplant outcomes in 2289 adult AML patients transplanted in first remission, between 2013 and 2017. Patients were stratified according to aELN into three groups: favorable (Fav, N = 181), intermediate (IM, N = 1185), and adverse (Adv, N = 923). Univariate analysis demonstrated significant differences in 2-year overall survival (OS) (Fav: 67.7%, IM: 64.9% and Adv: 53.9%; p < 0.001); disease-free survival (DFS) (Fav: 57.8%, IM: 55.5% and Adv: 45.3; p < 0.001) and relapse (Fav: 28%, IM: 27.5% and Adv: 37.5%; p < 0.001). Multivariate analysis (MVA) revealed no differences in outcomes between the Fav and IM groups, thus they were combined. On MVA, patients in the Adv risk group had the highest risk of relapse (HR 1.47 p <= 0.001) and inferior DFS (HR 1.35 p < 0.001) and OS (HR 1.39 p < 0.001), even using myeloablative conditioning or in those without the pre-HCT measurable-residual disease. Novel approaches to mitigate relapse in this high-risk group are urgently needed.
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| 4. |
- Kanate, Abraham S., et al.
(författare)
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Reduced-intensity transplantation for lymphomas using haploidentical related donors vs HLA-matched unrelated donors
- 2016
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Ingår i: Blood. - : American Society of Hematology. - 0006-4971 .- 1528-0020. ; 127:7, s. 938-947
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Tidskriftsartikel (refereegranskat)abstract
- We evaluated 917 adult lymphoma patients who received haploidentical (n = 185) or HLA-matched unrelated donor (URD) transplantation either with (n = 241) or without antithymocyte globulin (ATG; n = 491) following reduced-intensity conditioning regimens. Haploidentical recipients received posttransplant cyclophosphamide-based graft-versus-host disease (GVHD) prophylaxis, whereas URD recipients received calcineurin inhibitor-based prophylaxis. Median follow-up of survivors was 3 years. The 100-day cumulative incidence of grade III-IV acute GVHD on univariate analysis was 8%, 12%, and 17% in the haploidentical, URD without ATG, and URD with ATG groups, respectively (P = .44). Corresponding 1-year rates of chronic GVHD on univariate analysis were 13%, 51%, and 33%, respectively (P < .001). On multivariate analysis, grade III-IV acute GVHD was higher in URD without ATG (P = .001), as well as URD with ATG (P = .01), relative to haploidentical transplants. Similarly, relative to haploidentical transplants, risk of chronic GVHD was higher in URD without ATG and URD with ATG (P < .0001). Cumulative incidence of relapse/progression at 3 years was 36%, 28%, and 36% in the haploidentical, URD without ATG, and URD with ATG groups, respectively (P = .07). Corresponding 3-year overall survival (OS) was 60%, 62%, and 50% in the 3 groups, respectively, with multivariate analysis showing no survival difference between URD without ATG (P = .21) or URD with ATG (P = .16), relative to haploidentical transplants. Multivariate analysis showed no difference between the 3 groups in terms of nonrelapse mortality (NRM), relapse/progression, and progression-free survival (PFS). These data suggest that reduced-intensity conditioning haploidentical transplantation with posttransplant cyclophosphamide does not compromise early survival outcomes compared with matched URD transplantation, and is associated with significantly reduced risk of chronic GVHD.
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| 5. |
- Klyuchnikov, Evgeny, et al.
(författare)
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Reduced-Intensity Allografting as First Transplantation Approach in Relapsed/Refractory Grades One and Two Follicular Lymphoma Provides Improved Outcomes in Long-Term Survivors
- 2015
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Ingår i: Biology of blood and marrow transplantation. - : Elsevier BV. - 1083-8791 .- 1523-6536. ; 21:12, s. 2091-2099
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Tidskriftsartikel (refereegranskat)abstract
- This study was conducted to compare long-term outcomes in patients with refractory/relapsed grades 1 and 2 follicular lymphoma (FL) after allogeneic (allo) versus autologous (auto) hematopoietic cell transplantation (HCT) in the rituximab era. Adult patients with relapsed/refractory grades 1 and 2 FL undergoing first reduced-intensity allo-HCT or first autograft during 2000 to 2012 were evaluated. A total of 518 rituximab-treated patients were included. Allo-HCT patients were younger and more heavily pretreated, and more patients had advanced stage and chemoresistant disease. The 5-year adjusted probabilities, comparing auto-HCT versus allo-HCT groups for nonrelapse mortality (NRM) were 5% versus 26% (P <.0001); relapse/progression: 54% versus 20% (P <.0001); progression-free survival (PFS): 41% versus 58% (P <.001), and overall survival (OS): 74% versus 66% (P =.05). Auto-HCT was associated with a higher risk of relapse/progression beyond 5 months after HCT (relative risk [RR], 4.4; P <.0001) and worse PFS (RR, 2.9; P <.0001) beyond 11 months after HCT. In the first 24 months after HO', auto-HCT was associated with improved OS (RR,.41; P <.0001), but beyond 24 months, it was associated with inferior OS (RR, 2.2; P =.006). A landmark analysis of patients alive and progression-free at 2 years after HO' confirmed these observations, showing no difference in further NRM between both groups, but there was significantly higher risk of relapse/progression (RR, 7.3; P <.0001) and inferior PFS (RR, 3.2; P <.0001) and OS (RR, 2.1; P =.04) after auto-HCT. The 10-year cumulative incidences of second hematological malignancies after allo-HCT and auto-HCT were 0% and 7%, respectively. Auto-HCT and reduced-intensity conditioned allo-HCT as first transplantation approach can provide durable disease control in grades 1 and 2 FL patients. Continued disease relapse risk after auto-HCT translates into improved PFS and OS after allo-HCT in long-term survivors.
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| 6. |
- Wieduwilt, Matthew J., et al.
(författare)
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Haploidentical vs sibling, unrelated, or cord blood hematopoietic cell transplantation for acute lymphoblastic leukemia
- 2022
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Ingår i: Blood Advances. - : American Society of Hematology. - 2473-9529 .- 2473-9537. ; 6:1, s. 339-357
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Tidskriftsartikel (refereegranskat)abstract
- The role of haploidentical hematopoietic cell transplantation (HCT) using posttransplant cyclophosphamide (PTCy) for acute lymphoblastic leukemia (ALL) is being defined. We performed a retrospective, multivariable analysis comparing outcomes of HCT approaches by donor for adults with ALL in remission. The primary objective was to compare overall survival (OS) among haploidentical HCTs using PTCy and HLA-matched sibling donor (MSD), 8/8 HLAmatched unrelated donor (MUD), 7 /8 HLA-MUD, or umbilical cord blood (UCB) HCT. Comparing haploidentical HCT to MSD HCT, we found that OS, leukemia-free survival (LFS), nonrelapse mortality (NRM), relapse, and acute graft-versus-host disease (aGVHD) were not different but chronic GVHD (cGVHD) was higher in MSD HCT. Compared with MUD HCT, OS, LFS, and relapse were not different, but MUD HCT had increased NRM (hazard ratio [HR], 1.42; P = .02), grade 3 to 4 aGVHD (HR, 1.59; P = .005), and cGVHD. Compared with 7/8 UD HCT, LFS and relapse were not different, but 7/8 UD HCT had worse OS (HR, 1.38; P = .01) and increased NRM (HR, 2.13; P <_ .001), grade 3 to 4 aGVHD (HR, 1.86; P = .003), and cGVHD (HR, 1.72; P <_ .001). Compared with UCB HCT, late OS, late LFS, relapse, and cGVHD were not different but UCB HCT had worse early OS (<_18 months; HR, 1.93; P < .001), worse early LFS (HR, 1.40; P = .007) and increased incidences of NRM (HR, 2.08; P < .001) and grade 3 to 4 aGVHD (HR, 1.97; P < .001). Haploidentical HCT using PTCy showed no difference in survival but less GVHD compared with traditional MSD and MUD HCT and is the preferred alternative donor HCT option for adults with ALL in complete remission.
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