Reduced-Intensity Allografting as First Transplantation Approach in Relapsed/Refractory Grades One and Two Follicular Lymphoma Provides Improved Outcomes in Long-Term Survivors

Evgeny Klyuchnikov; Ulrike Bacher; Nicolaus M. Kröger; Parameswaran N. Hari; Kwang Woo Ahn; Jeanette Carreras; Veronika Bachanova; Asad Bashey; Jonathon B. Cohen; Anita D'Souza; César O. Freytes; Robert Peter Gale; Siddhartha Ganguly; Mark S. Hertzberg; Leona A. Holmberg; Mohamed A. Kharfan-Dabaja; Andreas Klein; Grace H. Ku; Ginna G. Laport; Hillard M. Lazarus; Alan M. Miller; Alberto Mussetti; Richard F. Olsson; Shimon Slavin; Saad Z. Usmani; Ravi Vij; William A. Wood; David G. Maloney; Anna M. Sureda; Sonali M. Smith; Mehdi Hamadani

doi:10.1016/j.bbmt.2015.07.028

Reduced-Intensity Allografting as First Transplantation Approach in Relapsed/Refractory Grades One and Two Follicular Lymphoma Provides Improved Outcomes in Long-Term Survivors

Evgeny Klyuchnikov, Ulrike Bacher, Nicolaus M. Kröger, Parameswaran N. Hari, Kwang Woo Ahn, Jeanette Carreras, Veronika Bachanova, Asad Bashey, Jonathon B. Cohen, Anita D'Souza, César O. Freytes, Robert Peter Gale, Siddhartha Ganguly, Mark S. Hertzberg, Leona A. Holmberg, Mohamed A. Kharfan-Dabaja, Andreas Klein, Grace H. Ku, Ginna G. Laport, Hillard M. LazarusAlan M. Miller, Alberto Mussetti, Richard F. Olsson, Shimon Slavin, Saad Z. Usmani, Ravi Vij, William A. Wood, David G. Maloney, Anna M. Sureda, Sonali M. Smith, Mehdi Hamadani

Medicine

Research output: Contribution to journal › Article

33 Scopus citations

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 HCT, 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 HCT 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.

Original language	English (US)
Pages (from-to)	2091-2099
Number of pages	9
Journal	Biology of Blood and Marrow Transplantation
Volume	21
Issue number	12
DOIs	https://doi.org/10.1016/j.bbmt.2015.07.028
State	Published - Dec 1 2015

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Keywords

Autologous hematopoietic cell transplantation
Grade 1 and 2 follicular lymphoma
Long-time survival
Reduced-intensity allogeneic hematopoietic cell transplantation

ASJC Scopus subject areas

Transplantation
Hematology

Cite this

Klyuchnikov, E., Bacher, U., Kröger, N. M., Hari, P. N., Ahn, K. W., Carreras, J., Bachanova, V., Bashey, A., Cohen, J. B., D'Souza, A., Freytes, C. O., Gale, R. P., Ganguly, S., Hertzberg, M. S., Holmberg, L. A., Kharfan-Dabaja, M. A., Klein, A., Ku, G. H., Laport, G. G., ... Hamadani, M. (2015). Reduced-Intensity Allografting as First Transplantation Approach in Relapsed/Refractory Grades One and Two Follicular Lymphoma Provides Improved Outcomes in Long-Term Survivors. Biology of Blood and Marrow Transplantation, 21(12), 2091-2099. https://doi.org/10.1016/j.bbmt.2015.07.028

Reduced-Intensity Allografting as First Transplantation Approach in Relapsed/Refractory Grades One and Two Follicular Lymphoma Provides Improved Outcomes in Long-Term Survivors. / Klyuchnikov, Evgeny; Bacher, Ulrike; Kröger, Nicolaus M.; Hari, Parameswaran N.; Ahn, Kwang Woo; Carreras, Jeanette; Bachanova, Veronika; Bashey, Asad; Cohen, Jonathon B.; D'Souza, Anita; Freytes, César O.; Gale, Robert Peter; Ganguly, Siddhartha; Hertzberg, Mark S.; Holmberg, Leona A.; Kharfan-Dabaja, Mohamed A.; Klein, Andreas; Ku, Grace H.; Laport, Ginna G.; Lazarus, Hillard M.; Miller, Alan M.; Mussetti, Alberto; Olsson, Richard F.; Slavin, Shimon; Usmani, Saad Z.; Vij, Ravi; Wood, William A.; Maloney, David G.; Sureda, Anna M.; Smith, Sonali M.; Hamadani, Mehdi.

In: Biology of Blood and Marrow Transplantation, Vol. 21, No. 12, 01.12.2015, p. 2091-2099.

Research output: Contribution to journal › Article

Klyuchnikov, E, Bacher, U, Kröger, NM, Hari, PN, Ahn, KW, Carreras, J, Bachanova, V, Bashey, A, Cohen, JB, D'Souza, A, Freytes, CO, Gale, RP, Ganguly, S, Hertzberg, MS, Holmberg, LA, Kharfan-Dabaja, MA, Klein, A, Ku, GH, Laport, GG, Lazarus, HM, Miller, AM, Mussetti, A, Olsson, RF, Slavin, S, Usmani, SZ, Vij, R, Wood, WA, Maloney, DG, Sureda, AM, Smith, SM & Hamadani, M 2015, 'Reduced-Intensity Allografting as First Transplantation Approach in Relapsed/Refractory Grades One and Two Follicular Lymphoma Provides Improved Outcomes in Long-Term Survivors', Biology of Blood and Marrow Transplantation, vol. 21, no. 12, pp. 2091-2099. https://doi.org/10.1016/j.bbmt.2015.07.028

Klyuchnikov, Evgeny ; Bacher, Ulrike ; Kröger, Nicolaus M. ; Hari, Parameswaran N. ; Ahn, Kwang Woo ; Carreras, Jeanette ; Bachanova, Veronika ; Bashey, Asad ; Cohen, Jonathon B. ; D'Souza, Anita ; Freytes, César O. ; Gale, Robert Peter ; Ganguly, Siddhartha ; Hertzberg, Mark S. ; Holmberg, Leona A. ; Kharfan-Dabaja, Mohamed A. ; Klein, Andreas ; Ku, Grace H. ; Laport, Ginna G. ; Lazarus, Hillard M. ; Miller, Alan M. ; Mussetti, Alberto ; Olsson, Richard F. ; Slavin, Shimon ; Usmani, Saad Z. ; Vij, Ravi ; Wood, William A. ; Maloney, David G. ; Sureda, Anna M. ; Smith, Sonali M. ; Hamadani, Mehdi. / Reduced-Intensity Allografting as First Transplantation Approach in Relapsed/Refractory Grades One and Two Follicular Lymphoma Provides Improved Outcomes in Long-Term Survivors. In: Biology of Blood and Marrow Transplantation. 2015 ; Vol. 21, No. 12. pp. 2091-2099.

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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 HCT, 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 HCT 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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author = "Evgeny Klyuchnikov and Ulrike Bacher and Kr{\"o}ger, {Nicolaus M.} and Hari, {Parameswaran N.} and Ahn, {Kwang Woo} and Jeanette Carreras and Veronika Bachanova and Asad Bashey and Cohen, {Jonathon B.} and Anita D'Souza and Freytes, {C{\'e}sar O.} and Gale, {Robert Peter} and Siddhartha Ganguly and Hertzberg, {Mark S.} and Holmberg, {Leona A.} and Kharfan-Dabaja, {Mohamed A.} and Andreas Klein and Ku, {Grace H.} and Laport, {Ginna G.} and Lazarus, {Hillard M.} and Miller, {Alan M.} and Alberto Mussetti and Olsson, {Richard F.} and Shimon Slavin and Usmani, {Saad Z.} and Ravi Vij and Wood, {William A.} and Maloney, {David G.} and Sureda, {Anna M.} and Smith, {Sonali M.} and Mehdi Hamadani",

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T1 - Reduced-Intensity Allografting as First Transplantation Approach in Relapsed/Refractory Grades One and Two Follicular Lymphoma Provides Improved Outcomes in Long-Term Survivors

AU - Klyuchnikov, Evgeny

AU - Bacher, Ulrike

AU - Kröger, Nicolaus M.

AU - Hari, Parameswaran N.

AU - Ahn, Kwang Woo

AU - Carreras, Jeanette

AU - Bachanova, Veronika

AU - Bashey, Asad

AU - Cohen, Jonathon B.

AU - D'Souza, Anita

AU - Freytes, César O.

AU - Gale, Robert Peter

AU - Ganguly, Siddhartha

AU - Hertzberg, Mark S.

AU - Holmberg, Leona A.

AU - Kharfan-Dabaja, Mohamed A.

AU - Klein, Andreas

AU - Ku, Grace H.

AU - Laport, Ginna G.

AU - Lazarus, Hillard M.

AU - Miller, Alan M.

AU - Mussetti, Alberto

AU - Olsson, Richard F.

AU - Slavin, Shimon

AU - Usmani, Saad Z.

AU - Vij, Ravi

AU - Wood, William A.

AU - Maloney, David G.

AU - Sureda, Anna M.

AU - Smith, Sonali M.

AU - Hamadani, Mehdi

PY - 2015/12/1

Y1 - 2015/12/1

N2 - 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 HCT, 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 HCT 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.

AB - 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 HCT, 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 HCT 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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KW - Reduced-intensity allogeneic hematopoietic cell transplantation

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10.1016/j.bbmt.2015.07.028