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Joseph H Antin - One of the best experts on this subject based on the ideXlab platform.

  • fludarabine busulfan versus fludarabine melphalan conditioning in patients undergoing reduced intensity conditioning hematopoietic stem cell transplantation for lymphoma
    Biology of Blood and Marrow Transplantation, 2016
    Co-Authors: Natasha Kekre, Francisco J Marquezmalaver, M Cabrero, Jl Pinana, Albert Esquirol, Robert J Soiffer, Dolores Caballero, Mariajose Terol, Rodrigo Martino, Joseph H Antin
    Abstract:

    There is at present little data to guide the choice of conditioning for patients with lymphoma undergoing reduced-intensity conditioning (RIC) allogeneic stem cell transplantation (SCT). In this study, we compared the outcomes of patients undergoing RIC SCT who received fludarabine and melphalan (FluMel), the standard RIC regimen used by the Spanish Group of Transplantation, and fludarabine and busulfan (FluBu), the standard RIC regimen used by the Dana-Farber Cancer Institute/Brigham and Women's Hospital. We analyzed 136 patients undergoing RIC SCT for lymphoma with either FluBu (n = 61) or FluMel (n = 75) conditioning between 2007 and 2014. Median follow-up was 36 months. The cumulative incidence of grades II to IV acute graft-versus-host disease (GVHD) was 13% with FluBu and 36% with FluMel (P = .002). The cumulative incidence of nonrelapse mortality (NRM) at 1 year was 3.3% with FluBu and 31% with FluMel (P < .0001). The cumulative incidence of relapse at 1 year was 29% with FluBu and 10% with FluMel (P = .08). The 3-year disease-free survival rate was 47% with FluBu and 36% with FluMel (P = .24), and the 3-year overall survival rate was 62% with FluBu and 48% with FluMel (P = .01). In multivariable analysis, FluMel was associated with a higher risk of acute grades II to IV GVHD (HR, 7.45; 95% CI, 2.30 to 24.17; P = .001) and higher risk of NRM (HR, 4.87; 95% CI, 1.36 to 17.44; P = .015). The type of conditioning was not significantly associated with relapse or disease-free survival in multivariable models. However, conditioning regimen was the only factor significantly associated with overall survival: FluMel conditioning was associated with a hazard ratio for death of 2.78 (95% CI, 1.23 to 6.27; P = .014) compared with FluBu. In conclusion, the use of FluBu as conditioning for patients undergoing SCT for lymphoma was associated with a lower risk of acute GVHD and NRM and improved overall survival when compared with FluMel in our retrospective study. These results confirm the differences between these RIC regimens in terms of toxicity and efficacy and support the need for comparative prospective studies.

  • fludarabine busulfan versus fludarabine melphalan conditioning in patients undergoing reduced intensity conditioning hematopoietic stem cell transplantation for lymphoma
    Biology of Blood and Marrow Transplantation, 2016
    Co-Authors: Natasha Kekre, Francisco J Marquezmalaver, M Cabrero, Jl Pinana, Albert Esquirol, Robert J Soiffer, Dolores Caballero, Mariajose Terol, Rodrigo Martino, Joseph H Antin
    Abstract:

    Abstract There is at present little data to guide the choice of conditioning for patients with lymphoma undergoing reduced-intensity conditioning (RIC) allogeneic stem cell transplantation (SCT). In this study, we compared the outcomes of patients undergoing RIC SCT who received fludarabine and melphalan (FluMel), the standard RIC regimen used by the Spanish Group of Transplantation, and fludarabine and busulfan (FluBu), the standard RIC regimen used by the Dana-Farber Cancer Institute/Brigham and Women's Hospital. We analyzed 136 patients undergoing RIC SCT for lymphoma with either FluBu (n = 61) or FluMel (n = 75) conditioning between 2007 and 2014. Median follow-up was 36 months. The cumulative incidence of grades II to IV acute graft-versus-host disease (GVHD) was 13% with FluBu and 36% with FluMel ( P  = .002). The cumulative incidence of nonrelapse mortality (NRM) at 1 year was 3.3% with FluBu and 31% with FluMel ( P P  = .08). The 3-year disease-free survival rate was 47% with FluBu and 36% with FluMel ( P  = .24), and the 3-year overall survival rate was 62% with FluBu and 48% with FluMel ( P  = .01). In multivariable analysis, FluMel was associated with a higher risk of acute grades II to IV GVHD (HR, 7.45; 95% CI, 2.30 to 24.17; P  = .001) and higher risk of NRM (HR, 4.87; 95% CI, 1.36 to 17.44; P  = .015). The type of conditioning was not significantly associated with relapse or disease-free survival in multivariable models. However, conditioning regimen was the only factor significantly associated with overall survival: FluMel conditioning was associated with a hazard ratio for death of 2.78 (95% CI, 1.23 to 6.27; P  = .014) compared with FluBu. In conclusion, the use of FluBu as conditioning for patients undergoing SCT for lymphoma was associated with a lower risk of acute GVHD and NRM and improved overall survival when compared with FluMel in our retrospective study. These results confirm the differences between these RIC regimens in terms of toxicity and efficacy and support the need for comparative prospective studies.

  • fludarabine busulfan versus fludarabine melphalan conditioning in patients undergoing reduced intensity conditioning hematopoietic stem cell transplantation for lymphoma
    Biology of Blood and Marrow Transplantation, 2016
    Co-Authors: Natasha Kekre, Francisco J Marquezmalaver, M Cabrero, Jl Pinana, Albert Esquirol, Robert J Soiffer, Dolores Caballero, Mariajose Terol, Rodrigo Martino, Joseph H Antin
    Abstract:

    Abstract There is at present little data to guide the choice of conditioning for patients with lymphoma undergoing reduced-intensity conditioning (RIC) allogeneic stem cell transplantation (SCT). In this study, we compared the outcomes of patients undergoing RIC SCT who received fludarabine and melphalan (FluMel), the standard RIC regimen used by the Spanish Group of Transplantation, and fludarabine and busulfan (FluBu), the standard RIC regimen used by the Dana-Farber Cancer Institute/Brigham and Women's Hospital. We analyzed 136 patients undergoing RIC SCT for lymphoma with either FluBu (n = 61) or FluMel (n = 75) conditioning between 2007 and 2014. Median follow-up was 36 months. The cumulative incidence of grades II to IV acute graft-versus-host disease (GVHD) was 13% with FluBu and 36% with FluMel (P = .002). The cumulative incidence of nonrelapse mortality (NRM) at 1 year was 3.3% with FluBu and 31% with FluMel (P

  • the use of busulphan as compared to melphalan in combination with fludarabine in the reduced intensity conditioning improves overall survival in patients with lymphoma
    Blood, 2015
    Co-Authors: Natasha Kekre, Francisco J Marquezmalaver, M Cabrero, Jl Pinana, Albert Esquirol, Robert J Soiffer, Dolores Caballero, Mariajose Terol, Rodrigo Martino, Joseph H Antin
    Abstract:

    Background: While many studies have attempted to compare different GVHD prophylaxis within the reduced intensity conditioning allogeneic stem cell transplant setting (RIC SCT), few studies have been performed comparing different conditioning regimens. Due to the lack of evidence on the best RIC, the selection of the conditioning regimen is mainly based on the experience from each institution. In this study, we compared the outcomes of patients undergoing RIC SCT in 2 different settings: the Spanish Group of Transplantation (GETH), where fludarabine + melphalan (FluMel) has been the standard RIC in patients with lymphoid malignancies and Dana-Farber Cancer Institute/Brigham and Women's Hospital (DFCI/BWH), where fludarabine + busulphan (FluBu) is the standard RIC. Patients and methods: We analyzed the outcomes of 136 patients diagnosed with lymphoma undergoing RIC with either FluBu (n=61) or FluMel (n=75) in the GETH or at DFCI/BWH between 2007 and 2014. Patient characteristics are shown in table 1. The following variables were included into the multivariable analysis: type of conditioning, GVHD prophylaxis, type of donor, age, previous transplant, and disease risk index (DRI) based on diagnosis and disease status at transplant. Median follow-up was 36 months. Results: The cumulative incidence of grades 2-4 acute GVHD was 13% vs 36% among patients receiving FluBu vs FluMel, respectively (p=0.002). In multivariable analysis only the type of conditioning significantly influenced the risk of grades 2-4 aGVHD [HR with FluMel 7.35, (95% CI= 2.27-23.8), p=0.0008]. The cumulative risk of non-relapse mortality at 1 year was 3.3% vs 31% for FluBu vs FluMel, respectively (p<0.001). In multivariable analysis again only type of conditioning significantly influenced the risk of NRM [HR with FluMel 5.61, (95% CI= 1.57-20.03), p=0.007]. The 1y cumulative incidence of relapse was 29% with FluBu vs 10% with FluMel (p=0.08). In multivariable analysis, only prior transplantation and donor type were associated with the risk of relapse. The 3-year disease-free survival in patients receiving FluBu was 55%, vs 40% for those receiving FluMel (p=0.24). Only donor type was significant in the DFS in multivariable models. Finally, the 3y OS in the BuFlu group was 72% vs 50% for those receiving FluMel (p=0.01) (fig 1). Conditioning regimen was the only factor significantly associated with OS in multivariable analysis, HR with FluMel 2.87, (95% CI= 1.28-6.43), p=0.01]. Conclusion: In this retrospective study of patients who received a RIC SCT for lymphoma, the use of FluBu as compared to FluMel was associated with a significant decrease in non-relapse mortality and an improvement in overall survival. Acknowledging the limitations associated a retrospective study, but in the absence of prospective randomized data, our results lend support to the choice of FluBu as a conditioning regimen in this setting. | N= 136 | Flu-Bu (n= 61) | Flu-Mel (n= 75) | P | | --------------------------------------------------------------------------------- | ---------------------------------------------------------------- | ----------------------------------------------------------------- | ----- | | Sex (male) | 41 (67.2%) | 49 (65.3%) | 0.081 | | Age | 42 (SD: 12.3) | 48.2 (SD: 12.3) | 0.073 | | Diagnosis: - Hodgkin - NHL | 9 (14.8%) 52 (85.2%) | 26 (34.7%) 49 (65.3%) | 0.008 | | Type of donor: - Related - Unrelated | 25 (41.0%) 36 (59.0%) | 36 (48.0%) 39 (52.0%) | 0.413 | | Source of stem cells: -BM -PB | -- 61 (100%) | 2 (2.7%) 73 (97.3%) | 0.502 | | Dis status at trx: - CR - PR or active dis | 31 (50.8%) 30 (49.2%) | 38 (50.7%) 37 (49.3%) | 0.986 | | GVHD prophylaxis: - CNI-MTX - SIRO-TKR | 42 (68.9%) 19 (31.1%) | 34 (45.3%) 41 (54.7%) | 0.006 | | Cause of death: - GvHD - Infection - Relapse - Others | 3 (15.8%) 2 (10.5%) 12 (63.2%) 2 (10.5%) | 11 (28.9%) 8 (21.1%) 10 (26.3%) 9 (23.7%) | 0.114 | Table 1. ![Figure 1.][1] Figure 1. Disclosures Antin: Gentium SpA/Jazz Pharmaceuticals: Membership on an entity's Board of Directors or advisory committees. Armand: BMS: Research Funding; Sequenta, Inc.: Research Funding; Merck: Consultancy, Research Funding; Infinity: Consultancy, Research Funding. [1]: pending:yes

Natasha Kekre - One of the best experts on this subject based on the ideXlab platform.

  • fludarabine busulfan versus fludarabine melphalan conditioning in patients undergoing reduced intensity conditioning hematopoietic stem cell transplantation for lymphoma
    Biology of Blood and Marrow Transplantation, 2016
    Co-Authors: Natasha Kekre, Francisco J Marquezmalaver, M Cabrero, Jl Pinana, Albert Esquirol, Robert J Soiffer, Dolores Caballero, Mariajose Terol, Rodrigo Martino, Joseph H Antin
    Abstract:

    There is at present little data to guide the choice of conditioning for patients with lymphoma undergoing reduced-intensity conditioning (RIC) allogeneic stem cell transplantation (SCT). In this study, we compared the outcomes of patients undergoing RIC SCT who received fludarabine and melphalan (FluMel), the standard RIC regimen used by the Spanish Group of Transplantation, and fludarabine and busulfan (FluBu), the standard RIC regimen used by the Dana-Farber Cancer Institute/Brigham and Women's Hospital. We analyzed 136 patients undergoing RIC SCT for lymphoma with either FluBu (n = 61) or FluMel (n = 75) conditioning between 2007 and 2014. Median follow-up was 36 months. The cumulative incidence of grades II to IV acute graft-versus-host disease (GVHD) was 13% with FluBu and 36% with FluMel (P = .002). The cumulative incidence of nonrelapse mortality (NRM) at 1 year was 3.3% with FluBu and 31% with FluMel (P < .0001). The cumulative incidence of relapse at 1 year was 29% with FluBu and 10% with FluMel (P = .08). The 3-year disease-free survival rate was 47% with FluBu and 36% with FluMel (P = .24), and the 3-year overall survival rate was 62% with FluBu and 48% with FluMel (P = .01). In multivariable analysis, FluMel was associated with a higher risk of acute grades II to IV GVHD (HR, 7.45; 95% CI, 2.30 to 24.17; P = .001) and higher risk of NRM (HR, 4.87; 95% CI, 1.36 to 17.44; P = .015). The type of conditioning was not significantly associated with relapse or disease-free survival in multivariable models. However, conditioning regimen was the only factor significantly associated with overall survival: FluMel conditioning was associated with a hazard ratio for death of 2.78 (95% CI, 1.23 to 6.27; P = .014) compared with FluBu. In conclusion, the use of FluBu as conditioning for patients undergoing SCT for lymphoma was associated with a lower risk of acute GVHD and NRM and improved overall survival when compared with FluMel in our retrospective study. These results confirm the differences between these RIC regimens in terms of toxicity and efficacy and support the need for comparative prospective studies.

  • fludarabine busulfan versus fludarabine melphalan conditioning in patients undergoing reduced intensity conditioning hematopoietic stem cell transplantation for lymphoma
    Biology of Blood and Marrow Transplantation, 2016
    Co-Authors: Natasha Kekre, Francisco J Marquezmalaver, M Cabrero, Jl Pinana, Albert Esquirol, Robert J Soiffer, Dolores Caballero, Mariajose Terol, Rodrigo Martino, Joseph H Antin
    Abstract:

    Abstract There is at present little data to guide the choice of conditioning for patients with lymphoma undergoing reduced-intensity conditioning (RIC) allogeneic stem cell transplantation (SCT). In this study, we compared the outcomes of patients undergoing RIC SCT who received fludarabine and melphalan (FluMel), the standard RIC regimen used by the Spanish Group of Transplantation, and fludarabine and busulfan (FluBu), the standard RIC regimen used by the Dana-Farber Cancer Institute/Brigham and Women's Hospital. We analyzed 136 patients undergoing RIC SCT for lymphoma with either FluBu (n = 61) or FluMel (n = 75) conditioning between 2007 and 2014. Median follow-up was 36 months. The cumulative incidence of grades II to IV acute graft-versus-host disease (GVHD) was 13% with FluBu and 36% with FluMel ( P  = .002). The cumulative incidence of nonrelapse mortality (NRM) at 1 year was 3.3% with FluBu and 31% with FluMel ( P P  = .08). The 3-year disease-free survival rate was 47% with FluBu and 36% with FluMel ( P  = .24), and the 3-year overall survival rate was 62% with FluBu and 48% with FluMel ( P  = .01). In multivariable analysis, FluMel was associated with a higher risk of acute grades II to IV GVHD (HR, 7.45; 95% CI, 2.30 to 24.17; P  = .001) and higher risk of NRM (HR, 4.87; 95% CI, 1.36 to 17.44; P  = .015). The type of conditioning was not significantly associated with relapse or disease-free survival in multivariable models. However, conditioning regimen was the only factor significantly associated with overall survival: FluMel conditioning was associated with a hazard ratio for death of 2.78 (95% CI, 1.23 to 6.27; P  = .014) compared with FluBu. In conclusion, the use of FluBu as conditioning for patients undergoing SCT for lymphoma was associated with a lower risk of acute GVHD and NRM and improved overall survival when compared with FluMel in our retrospective study. These results confirm the differences between these RIC regimens in terms of toxicity and efficacy and support the need for comparative prospective studies.

  • fludarabine busulfan versus fludarabine melphalan conditioning in patients undergoing reduced intensity conditioning hematopoietic stem cell transplantation for lymphoma
    Biology of Blood and Marrow Transplantation, 2016
    Co-Authors: Natasha Kekre, Francisco J Marquezmalaver, M Cabrero, Jl Pinana, Albert Esquirol, Robert J Soiffer, Dolores Caballero, Mariajose Terol, Rodrigo Martino, Joseph H Antin
    Abstract:

    Abstract There is at present little data to guide the choice of conditioning for patients with lymphoma undergoing reduced-intensity conditioning (RIC) allogeneic stem cell transplantation (SCT). In this study, we compared the outcomes of patients undergoing RIC SCT who received fludarabine and melphalan (FluMel), the standard RIC regimen used by the Spanish Group of Transplantation, and fludarabine and busulfan (FluBu), the standard RIC regimen used by the Dana-Farber Cancer Institute/Brigham and Women's Hospital. We analyzed 136 patients undergoing RIC SCT for lymphoma with either FluBu (n = 61) or FluMel (n = 75) conditioning between 2007 and 2014. Median follow-up was 36 months. The cumulative incidence of grades II to IV acute graft-versus-host disease (GVHD) was 13% with FluBu and 36% with FluMel (P = .002). The cumulative incidence of nonrelapse mortality (NRM) at 1 year was 3.3% with FluBu and 31% with FluMel (P

  • the use of busulphan as compared to melphalan in combination with fludarabine in the reduced intensity conditioning improves overall survival in patients with lymphoma
    Blood, 2015
    Co-Authors: Natasha Kekre, Francisco J Marquezmalaver, M Cabrero, Jl Pinana, Albert Esquirol, Robert J Soiffer, Dolores Caballero, Mariajose Terol, Rodrigo Martino, Joseph H Antin
    Abstract:

    Background: While many studies have attempted to compare different GVHD prophylaxis within the reduced intensity conditioning allogeneic stem cell transplant setting (RIC SCT), few studies have been performed comparing different conditioning regimens. Due to the lack of evidence on the best RIC, the selection of the conditioning regimen is mainly based on the experience from each institution. In this study, we compared the outcomes of patients undergoing RIC SCT in 2 different settings: the Spanish Group of Transplantation (GETH), where fludarabine + melphalan (FluMel) has been the standard RIC in patients with lymphoid malignancies and Dana-Farber Cancer Institute/Brigham and Women's Hospital (DFCI/BWH), where fludarabine + busulphan (FluBu) is the standard RIC. Patients and methods: We analyzed the outcomes of 136 patients diagnosed with lymphoma undergoing RIC with either FluBu (n=61) or FluMel (n=75) in the GETH or at DFCI/BWH between 2007 and 2014. Patient characteristics are shown in table 1. The following variables were included into the multivariable analysis: type of conditioning, GVHD prophylaxis, type of donor, age, previous transplant, and disease risk index (DRI) based on diagnosis and disease status at transplant. Median follow-up was 36 months. Results: The cumulative incidence of grades 2-4 acute GVHD was 13% vs 36% among patients receiving FluBu vs FluMel, respectively (p=0.002). In multivariable analysis only the type of conditioning significantly influenced the risk of grades 2-4 aGVHD [HR with FluMel 7.35, (95% CI= 2.27-23.8), p=0.0008]. The cumulative risk of non-relapse mortality at 1 year was 3.3% vs 31% for FluBu vs FluMel, respectively (p<0.001). In multivariable analysis again only type of conditioning significantly influenced the risk of NRM [HR with FluMel 5.61, (95% CI= 1.57-20.03), p=0.007]. The 1y cumulative incidence of relapse was 29% with FluBu vs 10% with FluMel (p=0.08). In multivariable analysis, only prior transplantation and donor type were associated with the risk of relapse. The 3-year disease-free survival in patients receiving FluBu was 55%, vs 40% for those receiving FluMel (p=0.24). Only donor type was significant in the DFS in multivariable models. Finally, the 3y OS in the BuFlu group was 72% vs 50% for those receiving FluMel (p=0.01) (fig 1). Conditioning regimen was the only factor significantly associated with OS in multivariable analysis, HR with FluMel 2.87, (95% CI= 1.28-6.43), p=0.01]. Conclusion: In this retrospective study of patients who received a RIC SCT for lymphoma, the use of FluBu as compared to FluMel was associated with a significant decrease in non-relapse mortality and an improvement in overall survival. Acknowledging the limitations associated a retrospective study, but in the absence of prospective randomized data, our results lend support to the choice of FluBu as a conditioning regimen in this setting. | N= 136 | Flu-Bu (n= 61) | Flu-Mel (n= 75) | P | | --------------------------------------------------------------------------------- | ---------------------------------------------------------------- | ----------------------------------------------------------------- | ----- | | Sex (male) | 41 (67.2%) | 49 (65.3%) | 0.081 | | Age | 42 (SD: 12.3) | 48.2 (SD: 12.3) | 0.073 | | Diagnosis: - Hodgkin - NHL | 9 (14.8%) 52 (85.2%) | 26 (34.7%) 49 (65.3%) | 0.008 | | Type of donor: - Related - Unrelated | 25 (41.0%) 36 (59.0%) | 36 (48.0%) 39 (52.0%) | 0.413 | | Source of stem cells: -BM -PB | -- 61 (100%) | 2 (2.7%) 73 (97.3%) | 0.502 | | Dis status at trx: - CR - PR or active dis | 31 (50.8%) 30 (49.2%) | 38 (50.7%) 37 (49.3%) | 0.986 | | GVHD prophylaxis: - CNI-MTX - SIRO-TKR | 42 (68.9%) 19 (31.1%) | 34 (45.3%) 41 (54.7%) | 0.006 | | Cause of death: - GvHD - Infection - Relapse - Others | 3 (15.8%) 2 (10.5%) 12 (63.2%) 2 (10.5%) | 11 (28.9%) 8 (21.1%) 10 (26.3%) 9 (23.7%) | 0.114 | Table 1. ![Figure 1.][1] Figure 1. Disclosures Antin: Gentium SpA/Jazz Pharmaceuticals: Membership on an entity's Board of Directors or advisory committees. Armand: BMS: Research Funding; Sequenta, Inc.: Research Funding; Merck: Consultancy, Research Funding; Infinity: Consultancy, Research Funding. [1]: pending:yes

Francisco J Marquezmalaver - One of the best experts on this subject based on the ideXlab platform.

  • fludarabine busulfan versus fludarabine melphalan conditioning in patients undergoing reduced intensity conditioning hematopoietic stem cell transplantation for lymphoma
    Biology of Blood and Marrow Transplantation, 2016
    Co-Authors: Natasha Kekre, Francisco J Marquezmalaver, M Cabrero, Jl Pinana, Albert Esquirol, Robert J Soiffer, Dolores Caballero, Mariajose Terol, Rodrigo Martino, Joseph H Antin
    Abstract:

    There is at present little data to guide the choice of conditioning for patients with lymphoma undergoing reduced-intensity conditioning (RIC) allogeneic stem cell transplantation (SCT). In this study, we compared the outcomes of patients undergoing RIC SCT who received fludarabine and melphalan (FluMel), the standard RIC regimen used by the Spanish Group of Transplantation, and fludarabine and busulfan (FluBu), the standard RIC regimen used by the Dana-Farber Cancer Institute/Brigham and Women's Hospital. We analyzed 136 patients undergoing RIC SCT for lymphoma with either FluBu (n = 61) or FluMel (n = 75) conditioning between 2007 and 2014. Median follow-up was 36 months. The cumulative incidence of grades II to IV acute graft-versus-host disease (GVHD) was 13% with FluBu and 36% with FluMel (P = .002). The cumulative incidence of nonrelapse mortality (NRM) at 1 year was 3.3% with FluBu and 31% with FluMel (P < .0001). The cumulative incidence of relapse at 1 year was 29% with FluBu and 10% with FluMel (P = .08). The 3-year disease-free survival rate was 47% with FluBu and 36% with FluMel (P = .24), and the 3-year overall survival rate was 62% with FluBu and 48% with FluMel (P = .01). In multivariable analysis, FluMel was associated with a higher risk of acute grades II to IV GVHD (HR, 7.45; 95% CI, 2.30 to 24.17; P = .001) and higher risk of NRM (HR, 4.87; 95% CI, 1.36 to 17.44; P = .015). The type of conditioning was not significantly associated with relapse or disease-free survival in multivariable models. However, conditioning regimen was the only factor significantly associated with overall survival: FluMel conditioning was associated with a hazard ratio for death of 2.78 (95% CI, 1.23 to 6.27; P = .014) compared with FluBu. In conclusion, the use of FluBu as conditioning for patients undergoing SCT for lymphoma was associated with a lower risk of acute GVHD and NRM and improved overall survival when compared with FluMel in our retrospective study. These results confirm the differences between these RIC regimens in terms of toxicity and efficacy and support the need for comparative prospective studies.

  • fludarabine busulfan versus fludarabine melphalan conditioning in patients undergoing reduced intensity conditioning hematopoietic stem cell transplantation for lymphoma
    Biology of Blood and Marrow Transplantation, 2016
    Co-Authors: Natasha Kekre, Francisco J Marquezmalaver, M Cabrero, Jl Pinana, Albert Esquirol, Robert J Soiffer, Dolores Caballero, Mariajose Terol, Rodrigo Martino, Joseph H Antin
    Abstract:

    Abstract There is at present little data to guide the choice of conditioning for patients with lymphoma undergoing reduced-intensity conditioning (RIC) allogeneic stem cell transplantation (SCT). In this study, we compared the outcomes of patients undergoing RIC SCT who received fludarabine and melphalan (FluMel), the standard RIC regimen used by the Spanish Group of Transplantation, and fludarabine and busulfan (FluBu), the standard RIC regimen used by the Dana-Farber Cancer Institute/Brigham and Women's Hospital. We analyzed 136 patients undergoing RIC SCT for lymphoma with either FluBu (n = 61) or FluMel (n = 75) conditioning between 2007 and 2014. Median follow-up was 36 months. The cumulative incidence of grades II to IV acute graft-versus-host disease (GVHD) was 13% with FluBu and 36% with FluMel ( P  = .002). The cumulative incidence of nonrelapse mortality (NRM) at 1 year was 3.3% with FluBu and 31% with FluMel ( P P  = .08). The 3-year disease-free survival rate was 47% with FluBu and 36% with FluMel ( P  = .24), and the 3-year overall survival rate was 62% with FluBu and 48% with FluMel ( P  = .01). In multivariable analysis, FluMel was associated with a higher risk of acute grades II to IV GVHD (HR, 7.45; 95% CI, 2.30 to 24.17; P  = .001) and higher risk of NRM (HR, 4.87; 95% CI, 1.36 to 17.44; P  = .015). The type of conditioning was not significantly associated with relapse or disease-free survival in multivariable models. However, conditioning regimen was the only factor significantly associated with overall survival: FluMel conditioning was associated with a hazard ratio for death of 2.78 (95% CI, 1.23 to 6.27; P  = .014) compared with FluBu. In conclusion, the use of FluBu as conditioning for patients undergoing SCT for lymphoma was associated with a lower risk of acute GVHD and NRM and improved overall survival when compared with FluMel in our retrospective study. These results confirm the differences between these RIC regimens in terms of toxicity and efficacy and support the need for comparative prospective studies.

  • fludarabine busulfan versus fludarabine melphalan conditioning in patients undergoing reduced intensity conditioning hematopoietic stem cell transplantation for lymphoma
    Biology of Blood and Marrow Transplantation, 2016
    Co-Authors: Natasha Kekre, Francisco J Marquezmalaver, M Cabrero, Jl Pinana, Albert Esquirol, Robert J Soiffer, Dolores Caballero, Mariajose Terol, Rodrigo Martino, Joseph H Antin
    Abstract:

    Abstract There is at present little data to guide the choice of conditioning for patients with lymphoma undergoing reduced-intensity conditioning (RIC) allogeneic stem cell transplantation (SCT). In this study, we compared the outcomes of patients undergoing RIC SCT who received fludarabine and melphalan (FluMel), the standard RIC regimen used by the Spanish Group of Transplantation, and fludarabine and busulfan (FluBu), the standard RIC regimen used by the Dana-Farber Cancer Institute/Brigham and Women's Hospital. We analyzed 136 patients undergoing RIC SCT for lymphoma with either FluBu (n = 61) or FluMel (n = 75) conditioning between 2007 and 2014. Median follow-up was 36 months. The cumulative incidence of grades II to IV acute graft-versus-host disease (GVHD) was 13% with FluBu and 36% with FluMel (P = .002). The cumulative incidence of nonrelapse mortality (NRM) at 1 year was 3.3% with FluBu and 31% with FluMel (P

  • the use of busulphan as compared to melphalan in combination with fludarabine in the reduced intensity conditioning improves overall survival in patients with lymphoma
    Blood, 2015
    Co-Authors: Natasha Kekre, Francisco J Marquezmalaver, M Cabrero, Jl Pinana, Albert Esquirol, Robert J Soiffer, Dolores Caballero, Mariajose Terol, Rodrigo Martino, Joseph H Antin
    Abstract:

    Background: While many studies have attempted to compare different GVHD prophylaxis within the reduced intensity conditioning allogeneic stem cell transplant setting (RIC SCT), few studies have been performed comparing different conditioning regimens. Due to the lack of evidence on the best RIC, the selection of the conditioning regimen is mainly based on the experience from each institution. In this study, we compared the outcomes of patients undergoing RIC SCT in 2 different settings: the Spanish Group of Transplantation (GETH), where fludarabine + melphalan (FluMel) has been the standard RIC in patients with lymphoid malignancies and Dana-Farber Cancer Institute/Brigham and Women's Hospital (DFCI/BWH), where fludarabine + busulphan (FluBu) is the standard RIC. Patients and methods: We analyzed the outcomes of 136 patients diagnosed with lymphoma undergoing RIC with either FluBu (n=61) or FluMel (n=75) in the GETH or at DFCI/BWH between 2007 and 2014. Patient characteristics are shown in table 1. The following variables were included into the multivariable analysis: type of conditioning, GVHD prophylaxis, type of donor, age, previous transplant, and disease risk index (DRI) based on diagnosis and disease status at transplant. Median follow-up was 36 months. Results: The cumulative incidence of grades 2-4 acute GVHD was 13% vs 36% among patients receiving FluBu vs FluMel, respectively (p=0.002). In multivariable analysis only the type of conditioning significantly influenced the risk of grades 2-4 aGVHD [HR with FluMel 7.35, (95% CI= 2.27-23.8), p=0.0008]. The cumulative risk of non-relapse mortality at 1 year was 3.3% vs 31% for FluBu vs FluMel, respectively (p<0.001). In multivariable analysis again only type of conditioning significantly influenced the risk of NRM [HR with FluMel 5.61, (95% CI= 1.57-20.03), p=0.007]. The 1y cumulative incidence of relapse was 29% with FluBu vs 10% with FluMel (p=0.08). In multivariable analysis, only prior transplantation and donor type were associated with the risk of relapse. The 3-year disease-free survival in patients receiving FluBu was 55%, vs 40% for those receiving FluMel (p=0.24). Only donor type was significant in the DFS in multivariable models. Finally, the 3y OS in the BuFlu group was 72% vs 50% for those receiving FluMel (p=0.01) (fig 1). Conditioning regimen was the only factor significantly associated with OS in multivariable analysis, HR with FluMel 2.87, (95% CI= 1.28-6.43), p=0.01]. Conclusion: In this retrospective study of patients who received a RIC SCT for lymphoma, the use of FluBu as compared to FluMel was associated with a significant decrease in non-relapse mortality and an improvement in overall survival. Acknowledging the limitations associated a retrospective study, but in the absence of prospective randomized data, our results lend support to the choice of FluBu as a conditioning regimen in this setting. | N= 136 | Flu-Bu (n= 61) | Flu-Mel (n= 75) | P | | --------------------------------------------------------------------------------- | ---------------------------------------------------------------- | ----------------------------------------------------------------- | ----- | | Sex (male) | 41 (67.2%) | 49 (65.3%) | 0.081 | | Age | 42 (SD: 12.3) | 48.2 (SD: 12.3) | 0.073 | | Diagnosis: - Hodgkin - NHL | 9 (14.8%) 52 (85.2%) | 26 (34.7%) 49 (65.3%) | 0.008 | | Type of donor: - Related - Unrelated | 25 (41.0%) 36 (59.0%) | 36 (48.0%) 39 (52.0%) | 0.413 | | Source of stem cells: -BM -PB | -- 61 (100%) | 2 (2.7%) 73 (97.3%) | 0.502 | | Dis status at trx: - CR - PR or active dis | 31 (50.8%) 30 (49.2%) | 38 (50.7%) 37 (49.3%) | 0.986 | | GVHD prophylaxis: - CNI-MTX - SIRO-TKR | 42 (68.9%) 19 (31.1%) | 34 (45.3%) 41 (54.7%) | 0.006 | | Cause of death: - GvHD - Infection - Relapse - Others | 3 (15.8%) 2 (10.5%) 12 (63.2%) 2 (10.5%) | 11 (28.9%) 8 (21.1%) 10 (26.3%) 9 (23.7%) | 0.114 | Table 1. ![Figure 1.][1] Figure 1. Disclosures Antin: Gentium SpA/Jazz Pharmaceuticals: Membership on an entity's Board of Directors or advisory committees. Armand: BMS: Research Funding; Sequenta, Inc.: Research Funding; Merck: Consultancy, Research Funding; Infinity: Consultancy, Research Funding. [1]: pending:yes

Jl Pinana - One of the best experts on this subject based on the ideXlab platform.

  • fludarabine busulfan versus fludarabine melphalan conditioning in patients undergoing reduced intensity conditioning hematopoietic stem cell transplantation for lymphoma
    Biology of Blood and Marrow Transplantation, 2016
    Co-Authors: Natasha Kekre, Francisco J Marquezmalaver, M Cabrero, Jl Pinana, Albert Esquirol, Robert J Soiffer, Dolores Caballero, Mariajose Terol, Rodrigo Martino, Joseph H Antin
    Abstract:

    There is at present little data to guide the choice of conditioning for patients with lymphoma undergoing reduced-intensity conditioning (RIC) allogeneic stem cell transplantation (SCT). In this study, we compared the outcomes of patients undergoing RIC SCT who received fludarabine and melphalan (FluMel), the standard RIC regimen used by the Spanish Group of Transplantation, and fludarabine and busulfan (FluBu), the standard RIC regimen used by the Dana-Farber Cancer Institute/Brigham and Women's Hospital. We analyzed 136 patients undergoing RIC SCT for lymphoma with either FluBu (n = 61) or FluMel (n = 75) conditioning between 2007 and 2014. Median follow-up was 36 months. The cumulative incidence of grades II to IV acute graft-versus-host disease (GVHD) was 13% with FluBu and 36% with FluMel (P = .002). The cumulative incidence of nonrelapse mortality (NRM) at 1 year was 3.3% with FluBu and 31% with FluMel (P < .0001). The cumulative incidence of relapse at 1 year was 29% with FluBu and 10% with FluMel (P = .08). The 3-year disease-free survival rate was 47% with FluBu and 36% with FluMel (P = .24), and the 3-year overall survival rate was 62% with FluBu and 48% with FluMel (P = .01). In multivariable analysis, FluMel was associated with a higher risk of acute grades II to IV GVHD (HR, 7.45; 95% CI, 2.30 to 24.17; P = .001) and higher risk of NRM (HR, 4.87; 95% CI, 1.36 to 17.44; P = .015). The type of conditioning was not significantly associated with relapse or disease-free survival in multivariable models. However, conditioning regimen was the only factor significantly associated with overall survival: FluMel conditioning was associated with a hazard ratio for death of 2.78 (95% CI, 1.23 to 6.27; P = .014) compared with FluBu. In conclusion, the use of FluBu as conditioning for patients undergoing SCT for lymphoma was associated with a lower risk of acute GVHD and NRM and improved overall survival when compared with FluMel in our retrospective study. These results confirm the differences between these RIC regimens in terms of toxicity and efficacy and support the need for comparative prospective studies.

  • fludarabine busulfan versus fludarabine melphalan conditioning in patients undergoing reduced intensity conditioning hematopoietic stem cell transplantation for lymphoma
    Biology of Blood and Marrow Transplantation, 2016
    Co-Authors: Natasha Kekre, Francisco J Marquezmalaver, M Cabrero, Jl Pinana, Albert Esquirol, Robert J Soiffer, Dolores Caballero, Mariajose Terol, Rodrigo Martino, Joseph H Antin
    Abstract:

    Abstract There is at present little data to guide the choice of conditioning for patients with lymphoma undergoing reduced-intensity conditioning (RIC) allogeneic stem cell transplantation (SCT). In this study, we compared the outcomes of patients undergoing RIC SCT who received fludarabine and melphalan (FluMel), the standard RIC regimen used by the Spanish Group of Transplantation, and fludarabine and busulfan (FluBu), the standard RIC regimen used by the Dana-Farber Cancer Institute/Brigham and Women's Hospital. We analyzed 136 patients undergoing RIC SCT for lymphoma with either FluBu (n = 61) or FluMel (n = 75) conditioning between 2007 and 2014. Median follow-up was 36 months. The cumulative incidence of grades II to IV acute graft-versus-host disease (GVHD) was 13% with FluBu and 36% with FluMel ( P  = .002). The cumulative incidence of nonrelapse mortality (NRM) at 1 year was 3.3% with FluBu and 31% with FluMel ( P P  = .08). The 3-year disease-free survival rate was 47% with FluBu and 36% with FluMel ( P  = .24), and the 3-year overall survival rate was 62% with FluBu and 48% with FluMel ( P  = .01). In multivariable analysis, FluMel was associated with a higher risk of acute grades II to IV GVHD (HR, 7.45; 95% CI, 2.30 to 24.17; P  = .001) and higher risk of NRM (HR, 4.87; 95% CI, 1.36 to 17.44; P  = .015). The type of conditioning was not significantly associated with relapse or disease-free survival in multivariable models. However, conditioning regimen was the only factor significantly associated with overall survival: FluMel conditioning was associated with a hazard ratio for death of 2.78 (95% CI, 1.23 to 6.27; P  = .014) compared with FluBu. In conclusion, the use of FluBu as conditioning for patients undergoing SCT for lymphoma was associated with a lower risk of acute GVHD and NRM and improved overall survival when compared with FluMel in our retrospective study. These results confirm the differences between these RIC regimens in terms of toxicity and efficacy and support the need for comparative prospective studies.

  • fludarabine busulfan versus fludarabine melphalan conditioning in patients undergoing reduced intensity conditioning hematopoietic stem cell transplantation for lymphoma
    Biology of Blood and Marrow Transplantation, 2016
    Co-Authors: Natasha Kekre, Francisco J Marquezmalaver, M Cabrero, Jl Pinana, Albert Esquirol, Robert J Soiffer, Dolores Caballero, Mariajose Terol, Rodrigo Martino, Joseph H Antin
    Abstract:

    Abstract There is at present little data to guide the choice of conditioning for patients with lymphoma undergoing reduced-intensity conditioning (RIC) allogeneic stem cell transplantation (SCT). In this study, we compared the outcomes of patients undergoing RIC SCT who received fludarabine and melphalan (FluMel), the standard RIC regimen used by the Spanish Group of Transplantation, and fludarabine and busulfan (FluBu), the standard RIC regimen used by the Dana-Farber Cancer Institute/Brigham and Women's Hospital. We analyzed 136 patients undergoing RIC SCT for lymphoma with either FluBu (n = 61) or FluMel (n = 75) conditioning between 2007 and 2014. Median follow-up was 36 months. The cumulative incidence of grades II to IV acute graft-versus-host disease (GVHD) was 13% with FluBu and 36% with FluMel (P = .002). The cumulative incidence of nonrelapse mortality (NRM) at 1 year was 3.3% with FluBu and 31% with FluMel (P

  • the use of busulphan as compared to melphalan in combination with fludarabine in the reduced intensity conditioning improves overall survival in patients with lymphoma
    Blood, 2015
    Co-Authors: Natasha Kekre, Francisco J Marquezmalaver, M Cabrero, Jl Pinana, Albert Esquirol, Robert J Soiffer, Dolores Caballero, Mariajose Terol, Rodrigo Martino, Joseph H Antin
    Abstract:

    Background: While many studies have attempted to compare different GVHD prophylaxis within the reduced intensity conditioning allogeneic stem cell transplant setting (RIC SCT), few studies have been performed comparing different conditioning regimens. Due to the lack of evidence on the best RIC, the selection of the conditioning regimen is mainly based on the experience from each institution. In this study, we compared the outcomes of patients undergoing RIC SCT in 2 different settings: the Spanish Group of Transplantation (GETH), where fludarabine + melphalan (FluMel) has been the standard RIC in patients with lymphoid malignancies and Dana-Farber Cancer Institute/Brigham and Women's Hospital (DFCI/BWH), where fludarabine + busulphan (FluBu) is the standard RIC. Patients and methods: We analyzed the outcomes of 136 patients diagnosed with lymphoma undergoing RIC with either FluBu (n=61) or FluMel (n=75) in the GETH or at DFCI/BWH between 2007 and 2014. Patient characteristics are shown in table 1. The following variables were included into the multivariable analysis: type of conditioning, GVHD prophylaxis, type of donor, age, previous transplant, and disease risk index (DRI) based on diagnosis and disease status at transplant. Median follow-up was 36 months. Results: The cumulative incidence of grades 2-4 acute GVHD was 13% vs 36% among patients receiving FluBu vs FluMel, respectively (p=0.002). In multivariable analysis only the type of conditioning significantly influenced the risk of grades 2-4 aGVHD [HR with FluMel 7.35, (95% CI= 2.27-23.8), p=0.0008]. The cumulative risk of non-relapse mortality at 1 year was 3.3% vs 31% for FluBu vs FluMel, respectively (p<0.001). In multivariable analysis again only type of conditioning significantly influenced the risk of NRM [HR with FluMel 5.61, (95% CI= 1.57-20.03), p=0.007]. The 1y cumulative incidence of relapse was 29% with FluBu vs 10% with FluMel (p=0.08). In multivariable analysis, only prior transplantation and donor type were associated with the risk of relapse. The 3-year disease-free survival in patients receiving FluBu was 55%, vs 40% for those receiving FluMel (p=0.24). Only donor type was significant in the DFS in multivariable models. Finally, the 3y OS in the BuFlu group was 72% vs 50% for those receiving FluMel (p=0.01) (fig 1). Conditioning regimen was the only factor significantly associated with OS in multivariable analysis, HR with FluMel 2.87, (95% CI= 1.28-6.43), p=0.01]. Conclusion: In this retrospective study of patients who received a RIC SCT for lymphoma, the use of FluBu as compared to FluMel was associated with a significant decrease in non-relapse mortality and an improvement in overall survival. Acknowledging the limitations associated a retrospective study, but in the absence of prospective randomized data, our results lend support to the choice of FluBu as a conditioning regimen in this setting. | N= 136 | Flu-Bu (n= 61) | Flu-Mel (n= 75) | P | | --------------------------------------------------------------------------------- | ---------------------------------------------------------------- | ----------------------------------------------------------------- | ----- | | Sex (male) | 41 (67.2%) | 49 (65.3%) | 0.081 | | Age | 42 (SD: 12.3) | 48.2 (SD: 12.3) | 0.073 | | Diagnosis: - Hodgkin - NHL | 9 (14.8%) 52 (85.2%) | 26 (34.7%) 49 (65.3%) | 0.008 | | Type of donor: - Related - Unrelated | 25 (41.0%) 36 (59.0%) | 36 (48.0%) 39 (52.0%) | 0.413 | | Source of stem cells: -BM -PB | -- 61 (100%) | 2 (2.7%) 73 (97.3%) | 0.502 | | Dis status at trx: - CR - PR or active dis | 31 (50.8%) 30 (49.2%) | 38 (50.7%) 37 (49.3%) | 0.986 | | GVHD prophylaxis: - CNI-MTX - SIRO-TKR | 42 (68.9%) 19 (31.1%) | 34 (45.3%) 41 (54.7%) | 0.006 | | Cause of death: - GvHD - Infection - Relapse - Others | 3 (15.8%) 2 (10.5%) 12 (63.2%) 2 (10.5%) | 11 (28.9%) 8 (21.1%) 10 (26.3%) 9 (23.7%) | 0.114 | Table 1. ![Figure 1.][1] Figure 1. Disclosures Antin: Gentium SpA/Jazz Pharmaceuticals: Membership on an entity's Board of Directors or advisory committees. Armand: BMS: Research Funding; Sequenta, Inc.: Research Funding; Merck: Consultancy, Research Funding; Infinity: Consultancy, Research Funding. [1]: pending:yes

Albert Esquirol - One of the best experts on this subject based on the ideXlab platform.

  • fludarabine busulfan versus fludarabine melphalan conditioning in patients undergoing reduced intensity conditioning hematopoietic stem cell transplantation for lymphoma
    Biology of Blood and Marrow Transplantation, 2016
    Co-Authors: Natasha Kekre, Francisco J Marquezmalaver, M Cabrero, Jl Pinana, Albert Esquirol, Robert J Soiffer, Dolores Caballero, Mariajose Terol, Rodrigo Martino, Joseph H Antin
    Abstract:

    There is at present little data to guide the choice of conditioning for patients with lymphoma undergoing reduced-intensity conditioning (RIC) allogeneic stem cell transplantation (SCT). In this study, we compared the outcomes of patients undergoing RIC SCT who received fludarabine and melphalan (FluMel), the standard RIC regimen used by the Spanish Group of Transplantation, and fludarabine and busulfan (FluBu), the standard RIC regimen used by the Dana-Farber Cancer Institute/Brigham and Women's Hospital. We analyzed 136 patients undergoing RIC SCT for lymphoma with either FluBu (n = 61) or FluMel (n = 75) conditioning between 2007 and 2014. Median follow-up was 36 months. The cumulative incidence of grades II to IV acute graft-versus-host disease (GVHD) was 13% with FluBu and 36% with FluMel (P = .002). The cumulative incidence of nonrelapse mortality (NRM) at 1 year was 3.3% with FluBu and 31% with FluMel (P < .0001). The cumulative incidence of relapse at 1 year was 29% with FluBu and 10% with FluMel (P = .08). The 3-year disease-free survival rate was 47% with FluBu and 36% with FluMel (P = .24), and the 3-year overall survival rate was 62% with FluBu and 48% with FluMel (P = .01). In multivariable analysis, FluMel was associated with a higher risk of acute grades II to IV GVHD (HR, 7.45; 95% CI, 2.30 to 24.17; P = .001) and higher risk of NRM (HR, 4.87; 95% CI, 1.36 to 17.44; P = .015). The type of conditioning was not significantly associated with relapse or disease-free survival in multivariable models. However, conditioning regimen was the only factor significantly associated with overall survival: FluMel conditioning was associated with a hazard ratio for death of 2.78 (95% CI, 1.23 to 6.27; P = .014) compared with FluBu. In conclusion, the use of FluBu as conditioning for patients undergoing SCT for lymphoma was associated with a lower risk of acute GVHD and NRM and improved overall survival when compared with FluMel in our retrospective study. These results confirm the differences between these RIC regimens in terms of toxicity and efficacy and support the need for comparative prospective studies.

  • fludarabine busulfan versus fludarabine melphalan conditioning in patients undergoing reduced intensity conditioning hematopoietic stem cell transplantation for lymphoma
    Biology of Blood and Marrow Transplantation, 2016
    Co-Authors: Natasha Kekre, Francisco J Marquezmalaver, M Cabrero, Jl Pinana, Albert Esquirol, Robert J Soiffer, Dolores Caballero, Mariajose Terol, Rodrigo Martino, Joseph H Antin
    Abstract:

    Abstract There is at present little data to guide the choice of conditioning for patients with lymphoma undergoing reduced-intensity conditioning (RIC) allogeneic stem cell transplantation (SCT). In this study, we compared the outcomes of patients undergoing RIC SCT who received fludarabine and melphalan (FluMel), the standard RIC regimen used by the Spanish Group of Transplantation, and fludarabine and busulfan (FluBu), the standard RIC regimen used by the Dana-Farber Cancer Institute/Brigham and Women's Hospital. We analyzed 136 patients undergoing RIC SCT for lymphoma with either FluBu (n = 61) or FluMel (n = 75) conditioning between 2007 and 2014. Median follow-up was 36 months. The cumulative incidence of grades II to IV acute graft-versus-host disease (GVHD) was 13% with FluBu and 36% with FluMel ( P  = .002). The cumulative incidence of nonrelapse mortality (NRM) at 1 year was 3.3% with FluBu and 31% with FluMel ( P P  = .08). The 3-year disease-free survival rate was 47% with FluBu and 36% with FluMel ( P  = .24), and the 3-year overall survival rate was 62% with FluBu and 48% with FluMel ( P  = .01). In multivariable analysis, FluMel was associated with a higher risk of acute grades II to IV GVHD (HR, 7.45; 95% CI, 2.30 to 24.17; P  = .001) and higher risk of NRM (HR, 4.87; 95% CI, 1.36 to 17.44; P  = .015). The type of conditioning was not significantly associated with relapse or disease-free survival in multivariable models. However, conditioning regimen was the only factor significantly associated with overall survival: FluMel conditioning was associated with a hazard ratio for death of 2.78 (95% CI, 1.23 to 6.27; P  = .014) compared with FluBu. In conclusion, the use of FluBu as conditioning for patients undergoing SCT for lymphoma was associated with a lower risk of acute GVHD and NRM and improved overall survival when compared with FluMel in our retrospective study. These results confirm the differences between these RIC regimens in terms of toxicity and efficacy and support the need for comparative prospective studies.

  • fludarabine busulfan versus fludarabine melphalan conditioning in patients undergoing reduced intensity conditioning hematopoietic stem cell transplantation for lymphoma
    Biology of Blood and Marrow Transplantation, 2016
    Co-Authors: Natasha Kekre, Francisco J Marquezmalaver, M Cabrero, Jl Pinana, Albert Esquirol, Robert J Soiffer, Dolores Caballero, Mariajose Terol, Rodrigo Martino, Joseph H Antin
    Abstract:

    Abstract There is at present little data to guide the choice of conditioning for patients with lymphoma undergoing reduced-intensity conditioning (RIC) allogeneic stem cell transplantation (SCT). In this study, we compared the outcomes of patients undergoing RIC SCT who received fludarabine and melphalan (FluMel), the standard RIC regimen used by the Spanish Group of Transplantation, and fludarabine and busulfan (FluBu), the standard RIC regimen used by the Dana-Farber Cancer Institute/Brigham and Women's Hospital. We analyzed 136 patients undergoing RIC SCT for lymphoma with either FluBu (n = 61) or FluMel (n = 75) conditioning between 2007 and 2014. Median follow-up was 36 months. The cumulative incidence of grades II to IV acute graft-versus-host disease (GVHD) was 13% with FluBu and 36% with FluMel (P = .002). The cumulative incidence of nonrelapse mortality (NRM) at 1 year was 3.3% with FluBu and 31% with FluMel (P

  • the use of busulphan as compared to melphalan in combination with fludarabine in the reduced intensity conditioning improves overall survival in patients with lymphoma
    Blood, 2015
    Co-Authors: Natasha Kekre, Francisco J Marquezmalaver, M Cabrero, Jl Pinana, Albert Esquirol, Robert J Soiffer, Dolores Caballero, Mariajose Terol, Rodrigo Martino, Joseph H Antin
    Abstract:

    Background: While many studies have attempted to compare different GVHD prophylaxis within the reduced intensity conditioning allogeneic stem cell transplant setting (RIC SCT), few studies have been performed comparing different conditioning regimens. Due to the lack of evidence on the best RIC, the selection of the conditioning regimen is mainly based on the experience from each institution. In this study, we compared the outcomes of patients undergoing RIC SCT in 2 different settings: the Spanish Group of Transplantation (GETH), where fludarabine + melphalan (FluMel) has been the standard RIC in patients with lymphoid malignancies and Dana-Farber Cancer Institute/Brigham and Women's Hospital (DFCI/BWH), where fludarabine + busulphan (FluBu) is the standard RIC. Patients and methods: We analyzed the outcomes of 136 patients diagnosed with lymphoma undergoing RIC with either FluBu (n=61) or FluMel (n=75) in the GETH or at DFCI/BWH between 2007 and 2014. Patient characteristics are shown in table 1. The following variables were included into the multivariable analysis: type of conditioning, GVHD prophylaxis, type of donor, age, previous transplant, and disease risk index (DRI) based on diagnosis and disease status at transplant. Median follow-up was 36 months. Results: The cumulative incidence of grades 2-4 acute GVHD was 13% vs 36% among patients receiving FluBu vs FluMel, respectively (p=0.002). In multivariable analysis only the type of conditioning significantly influenced the risk of grades 2-4 aGVHD [HR with FluMel 7.35, (95% CI= 2.27-23.8), p=0.0008]. The cumulative risk of non-relapse mortality at 1 year was 3.3% vs 31% for FluBu vs FluMel, respectively (p<0.001). In multivariable analysis again only type of conditioning significantly influenced the risk of NRM [HR with FluMel 5.61, (95% CI= 1.57-20.03), p=0.007]. The 1y cumulative incidence of relapse was 29% with FluBu vs 10% with FluMel (p=0.08). In multivariable analysis, only prior transplantation and donor type were associated with the risk of relapse. The 3-year disease-free survival in patients receiving FluBu was 55%, vs 40% for those receiving FluMel (p=0.24). Only donor type was significant in the DFS in multivariable models. Finally, the 3y OS in the BuFlu group was 72% vs 50% for those receiving FluMel (p=0.01) (fig 1). Conditioning regimen was the only factor significantly associated with OS in multivariable analysis, HR with FluMel 2.87, (95% CI= 1.28-6.43), p=0.01]. Conclusion: In this retrospective study of patients who received a RIC SCT for lymphoma, the use of FluBu as compared to FluMel was associated with a significant decrease in non-relapse mortality and an improvement in overall survival. Acknowledging the limitations associated a retrospective study, but in the absence of prospective randomized data, our results lend support to the choice of FluBu as a conditioning regimen in this setting. | N= 136 | Flu-Bu (n= 61) | Flu-Mel (n= 75) | P | | --------------------------------------------------------------------------------- | ---------------------------------------------------------------- | ----------------------------------------------------------------- | ----- | | Sex (male) | 41 (67.2%) | 49 (65.3%) | 0.081 | | Age | 42 (SD: 12.3) | 48.2 (SD: 12.3) | 0.073 | | Diagnosis: - Hodgkin - NHL | 9 (14.8%) 52 (85.2%) | 26 (34.7%) 49 (65.3%) | 0.008 | | Type of donor: - Related - Unrelated | 25 (41.0%) 36 (59.0%) | 36 (48.0%) 39 (52.0%) | 0.413 | | Source of stem cells: -BM -PB | -- 61 (100%) | 2 (2.7%) 73 (97.3%) | 0.502 | | Dis status at trx: - CR - PR or active dis | 31 (50.8%) 30 (49.2%) | 38 (50.7%) 37 (49.3%) | 0.986 | | GVHD prophylaxis: - CNI-MTX - SIRO-TKR | 42 (68.9%) 19 (31.1%) | 34 (45.3%) 41 (54.7%) | 0.006 | | Cause of death: - GvHD - Infection - Relapse - Others | 3 (15.8%) 2 (10.5%) 12 (63.2%) 2 (10.5%) | 11 (28.9%) 8 (21.1%) 10 (26.3%) 9 (23.7%) | 0.114 | Table 1. ![Figure 1.][1] Figure 1. Disclosures Antin: Gentium SpA/Jazz Pharmaceuticals: Membership on an entity's Board of Directors or advisory committees. Armand: BMS: Research Funding; Sequenta, Inc.: Research Funding; Merck: Consultancy, Research Funding; Infinity: Consultancy, Research Funding. [1]: pending:yes