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Your search keyword '"Nathan, Sunita"' showing total 18 results
Start Over Author "Nathan, Sunita" Publisher dokkyo med univ, dept hematol & oncol, mibu, tochigi, japan.
18 results on '"Nathan, Sunita"'

1. Haploidentical vs sibling, unrelated, or cord blood hematopoietic cell transplantation for acute lymphoblastic leukemia

Author

Wieduwilt, Matthew J., Metheny, Leland, Zhang, Mei-Jie, Wang, Hai-Lin, Estrada-Merly, Noel, Marks, David, I, Al-Homsi, A. Samer, Muffly, Lori, Chao, Nelson, Rizzieri, David, Gale, Robert Peter, Gadalla, Shahinaz M., Cairo, Mitchell, Mussetti, Alberto, Gore, Steven, Bhatt, Vijaya Raj, Patel, Sagar S., Michelis, Fotios, V, Inamoto, Yoshihiro, Badawy, Sherif M., Copelan, Edward, Palmisiano, Neil, Kharfan-Dabaja, Mohamed A., Lazarus, Hillard M., Ganguly, Siddhartha, Bredeson, Christopher, Diaz Perez, Miguel Angel, Cassaday, Ryan, Savani, Bipin N., Ballen, Karen, Martino, Rodrigo, Wirk, Baldeep, Bacher, Ulrike, Aljurf, Mahmoud, Bashey, Asad, Murthy, Hemant S., Yared, Jean A., Aldoss, Ibrahim, Farhadfar, Nosha, Liu, Hongtao, Abdel-Azim, Hisham, Waller, Edmund K., Solh, Melhem, Seftel, Matthew D., van der Poel, Marjolein, Grunwald, Michael R., Liesveld, Jane L., Kamble, Rammurti T., McGuirk, Joseph, Munker, Reinhold, Cahn, Jean-Yves, Lee, Jong Wook, Freytes, Cesar O., Krem, Maxwell M., Winestone, Lena E., Gergis, Usama, Nathan, Sunita, Olsson, Richard F., Verdonck, Leo F., Sharma, Akshay, Ringden, Olle, Friend, Brian D., Cerny, Jan, Choe, Hannah, Chhabra, Saurabh, Nishihori, Taiga, Seo, Sachiko, George, Biju, Baxter-Lowe, Lee Ann, Hildebrandt, Gerhard C., de Lima, Marcos, Litzow, Mark, Kebriaei, Partow, Hourigan, Christopher S., Abid, Muhammad Bilal, Weisdorf, Daniel J., Saber, Wael, Wieduwilt, Matthew J., Metheny, Leland, Zhang, Mei-Jie, Wang, Hai-Lin, Estrada-Merly, Noel, Marks, David, I, Al-Homsi, A. Samer, Muffly, Lori, Chao, Nelson, Rizzieri, David, Gale, Robert Peter, Gadalla, Shahinaz M., Cairo, Mitchell, Mussetti, Alberto, Gore, Steven, Bhatt, Vijaya Raj, Patel, Sagar S., Michelis, Fotios, V, Inamoto, Yoshihiro, Badawy, Sherif M., Copelan, Edward, Palmisiano, Neil, Kharfan-Dabaja, Mohamed A., Lazarus, Hillard M., Ganguly, Siddhartha, Bredeson, Christopher, Diaz Perez, Miguel Angel, Cassaday, Ryan, Savani, Bipin N., Ballen, Karen, Martino, Rodrigo, Wirk, Baldeep, Bacher, Ulrike, Aljurf, Mahmoud, Bashey, Asad, Murthy, Hemant S., Yared, Jean A., Aldoss, Ibrahim, Farhadfar, Nosha, Liu, Hongtao, Abdel-Azim, Hisham, Waller, Edmund K., Solh, Melhem, Seftel, Matthew D., van der Poel, Marjolein, Grunwald, Michael R., Liesveld, Jane L., Kamble, Rammurti T., McGuirk, Joseph, Munker, Reinhold, Cahn, Jean-Yves, Lee, Jong Wook, Freytes, Cesar O., Krem, Maxwell M., Winestone, Lena E., Gergis, Usama, Nathan, Sunita, Olsson, Richard F., Verdonck, Leo F., Sharma, Akshay, Ringden, Olle, Friend, Brian D., Cerny, Jan, Choe, Hannah, Chhabra, Saurabh, Nishihori, Taiga, Seo, Sachiko, George, Biju, Baxter-Lowe, Lee Ann, Hildebrandt, Gerhard C., de Lima, Marcos, Litzow, Mark, Kebriaei, Partow, Hourigan, Christopher S., Abid, Muhammad Bilal, Weisdorf, Daniel J., and Saber, Wael

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.

Published
2022
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2. Risk classification at diagnosis predicts post-HCT outcomes in intermediate-, adverse-risk, and KMT2A-rearranged AML

Author

Menghrajani, Kamal, Gomez-Arteaga, Alexandra, Madero-Marroquin, Rafael, Zhang, Mei-Jie, Bo-Subait, Khalid, Sanchez, Jonathan, Wang, Hai-Lin, Aljurf, Mahmoud, Assal, Amer, Bacher, Vera Ulrike, Badawy, Sherif M., Bejanyan, Nelli, Bhatt, Vijaya Raj, Bredeson, Christopher, Byrne, Michael, Castillo, Paul, Cerny, Jan, Chhabra, Saurabh, Ciurea, Stefan Octavian, DeFilipp, Zachariah, Farhadfar, Nosha, Gadalla, Shahinaz, Gale, Robert Peter, Ganguly, Siddhartha, Gowda, Lohith, Grunwald, Michael R., Hashmi, Shahrukh, Hildebrandt, Gerhard, Kanakry, Christopher G., Kansagra, Ankit, Khimani, Farhad, Krem, Maxwell, Lazarus, Hillard, Liu, Hongtao, Martino, Rodrigo, Michelis, Fotios, V, Nathan, Sunita, Nishihori, Taiga, Olsson, Richard, Reshef, Ran, Rizzieri, David, Rowe, Jacob M., Savani, Bipin N., Seo, Sachiko, Sharma, Akshay, Solh, Melhem, Ustun, Celalettin, Verdonck, Leo F., Hourigan, Christopher, Sandmaier, Brenda, Litzow, Mark, Kebriaei, Partow, Weisdorf, Daniel, Zhang, Yanming, Tallman, Martin S., Saber, Wael, Menghrajani, Kamal, Gomez-Arteaga, Alexandra, Madero-Marroquin, Rafael, Zhang, Mei-Jie, Bo-Subait, Khalid, Sanchez, Jonathan, Wang, Hai-Lin, Aljurf, Mahmoud, Assal, Amer, Bacher, Vera Ulrike, Badawy, Sherif M., Bejanyan, Nelli, Bhatt, Vijaya Raj, Bredeson, Christopher, Byrne, Michael, Castillo, Paul, Cerny, Jan, Chhabra, Saurabh, Ciurea, Stefan Octavian, DeFilipp, Zachariah, Farhadfar, Nosha, Gadalla, Shahinaz, Gale, Robert Peter, Ganguly, Siddhartha, Gowda, Lohith, Grunwald, Michael R., Hashmi, Shahrukh, Hildebrandt, Gerhard, Kanakry, Christopher G., Kansagra, Ankit, Khimani, Farhad, Krem, Maxwell, Lazarus, Hillard, Liu, Hongtao, Martino, Rodrigo, Michelis, Fotios, V, Nathan, Sunita, Nishihori, Taiga, Olsson, Richard, Reshef, Ran, Rizzieri, David, Rowe, Jacob M., Savani, Bipin N., Seo, Sachiko, Sharma, Akshay, Solh, Melhem, Ustun, Celalettin, Verdonck, Leo F., Hourigan, Christopher, Sandmaier, Brenda, Litzow, Mark, Kebriaei, Partow, Weisdorf, Daniel, Zhang, Yanming, Tallman, Martin S., and Saber, Wael

Abstract

Little is known about whether risk classification at diagnosis predicts post-hematopoietic cell transplantation (HCT) outcomes in patients with acute myeloid leukemia (AML). We evaluated 8709 patients with AML from the CIBMTR database, and after selection and manual curation of the cytogenetics data, 3779 patients in first complete remission were included in the final analysis: 2384 with intermediate-risk, 969 with adverse-risk, and 426 with KMT2A-rearranged disease. An adjusted multivariable analysis detected an increased risk of relapse for patients with KMT2A-rearranged or adverse-risk AML as compared to those with intermediate-risk disease (hazards ratio [HR], 1.27; P = .01; HR, 1.71; P < .001, respectively). Leukemia-free survival was similar for patients with KMT2A rearrangement or adverse risk (HR, 1.26; P = .002, and HR, 1.47; P < .001), as was overall survival (HR, 1.32; P < .001, and HR, 1.45; P < .001). No differences in outcome were detected when patients were stratified by KMT2A fusion partner. This study is the largest conducted to date on post-HCT outcomes in AML, with manually curated cytogenetics used for risk stratification. Our work demonstrates that risk classification at diagnosis remains predictive of post-HCT outcomes in AML. It also highlights the critical need to develop novel treatment strategies for patients with KMT2A-rearranged and adverse-risk disease.

Published
2022
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3. Haploidentical vs sibling, unrelated, or cord blood hematopoietic cell transplantation for acute lymphoblastic leukemia

Author

Wieduwilt, Matthew J., Metheny, Leland, Zhang, Mei-Jie, Wang, Hai-Lin, Estrada-Merly, Noel, Marks, David, I, Al-Homsi, A. Samer, Muffly, Lori, Chao, Nelson, Rizzieri, David, Gale, Robert Peter, Gadalla, Shahinaz M., Cairo, Mitchell, Mussetti, Alberto, Gore, Steven, Bhatt, Vijaya Raj, Patel, Sagar S., Michelis, Fotios, V, Inamoto, Yoshihiro, Badawy, Sherif M., Copelan, Edward, Palmisiano, Neil, Kharfan-Dabaja, Mohamed A., Lazarus, Hillard M., Ganguly, Siddhartha, Bredeson, Christopher, Diaz Perez, Miguel Angel, Cassaday, Ryan, Savani, Bipin N., Ballen, Karen, Martino, Rodrigo, Wirk, Baldeep, Bacher, Ulrike, Aljurf, Mahmoud, Bashey, Asad, Murthy, Hemant S., Yared, Jean A., Aldoss, Ibrahim, Farhadfar, Nosha, Liu, Hongtao, Abdel-Azim, Hisham, Waller, Edmund K., Solh, Melhem, Seftel, Matthew D., van der Poel, Marjolein, Grunwald, Michael R., Liesveld, Jane L., Kamble, Rammurti T., McGuirk, Joseph, Munker, Reinhold, Cahn, Jean-Yves, Lee, Jong Wook, Freytes, Cesar O., Krem, Maxwell M., Winestone, Lena E., Gergis, Usama, Nathan, Sunita, Olsson, Richard F., Verdonck, Leo F., Sharma, Akshay, Ringden, Olle, Friend, Brian D., Cerny, Jan, Choe, Hannah, Chhabra, Saurabh, Nishihori, Taiga, Seo, Sachiko, George, Biju, Baxter-Lowe, Lee Ann, Hildebrandt, Gerhard C., de Lima, Marcos, Litzow, Mark, Kebriaei, Partow, Hourigan, Christopher S., Abid, Muhammad Bilal, Weisdorf, Daniel J., Saber, Wael, Wieduwilt, Matthew J., Metheny, Leland, Zhang, Mei-Jie, Wang, Hai-Lin, Estrada-Merly, Noel, Marks, David, I, Al-Homsi, A. Samer, Muffly, Lori, Chao, Nelson, Rizzieri, David, Gale, Robert Peter, Gadalla, Shahinaz M., Cairo, Mitchell, Mussetti, Alberto, Gore, Steven, Bhatt, Vijaya Raj, Patel, Sagar S., Michelis, Fotios, V, Inamoto, Yoshihiro, Badawy, Sherif M., Copelan, Edward, Palmisiano, Neil, Kharfan-Dabaja, Mohamed A., Lazarus, Hillard M., Ganguly, Siddhartha, Bredeson, Christopher, Diaz Perez, Miguel Angel, Cassaday, Ryan, Savani, Bipin N., Ballen, Karen, Martino, Rodrigo, Wirk, Baldeep, Bacher, Ulrike, Aljurf, Mahmoud, Bashey, Asad, Murthy, Hemant S., Yared, Jean A., Aldoss, Ibrahim, Farhadfar, Nosha, Liu, Hongtao, Abdel-Azim, Hisham, Waller, Edmund K., Solh, Melhem, Seftel, Matthew D., van der Poel, Marjolein, Grunwald, Michael R., Liesveld, Jane L., Kamble, Rammurti T., McGuirk, Joseph, Munker, Reinhold, Cahn, Jean-Yves, Lee, Jong Wook, Freytes, Cesar O., Krem, Maxwell M., Winestone, Lena E., Gergis, Usama, Nathan, Sunita, Olsson, Richard F., Verdonck, Leo F., Sharma, Akshay, Ringden, Olle, Friend, Brian D., Cerny, Jan, Choe, Hannah, Chhabra, Saurabh, Nishihori, Taiga, Seo, Sachiko, George, Biju, Baxter-Lowe, Lee Ann, Hildebrandt, Gerhard C., de Lima, Marcos, Litzow, Mark, Kebriaei, Partow, Hourigan, Christopher S., Abid, Muhammad Bilal, Weisdorf, Daniel J., and Saber, Wael

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.

Published
2022
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4. Haploidentical vs sibling, unrelated, or cord blood hematopoietic cell transplantation for acute lymphoblastic leukemia

Author

Wieduwilt, Matthew J., Metheny, Leland, Zhang, Mei-Jie, Wang, Hai-Lin, Estrada-Merly, Noel, Marks, David, I, Al-Homsi, A. Samer, Muffly, Lori, Chao, Nelson, Rizzieri, David, Gale, Robert Peter, Gadalla, Shahinaz M., Cairo, Mitchell, Mussetti, Alberto, Gore, Steven, Bhatt, Vijaya Raj, Patel, Sagar S., Michelis, Fotios, V, Inamoto, Yoshihiro, Badawy, Sherif M., Copelan, Edward, Palmisiano, Neil, Kharfan-Dabaja, Mohamed A., Lazarus, Hillard M., Ganguly, Siddhartha, Bredeson, Christopher, Diaz Perez, Miguel Angel, Cassaday, Ryan, Savani, Bipin N., Ballen, Karen, Martino, Rodrigo, Wirk, Baldeep, Bacher, Ulrike, Aljurf, Mahmoud, Bashey, Asad, Murthy, Hemant S., Yared, Jean A., Aldoss, Ibrahim, Farhadfar, Nosha, Liu, Hongtao, Abdel-Azim, Hisham, Waller, Edmund K., Solh, Melhem, Seftel, Matthew D., van der Poel, Marjolein, Grunwald, Michael R., Liesveld, Jane L., Kamble, Rammurti T., McGuirk, Joseph, Munker, Reinhold, Cahn, Jean-Yves, Lee, Jong Wook, Freytes, Cesar O., Krem, Maxwell M., Winestone, Lena E., Gergis, Usama, Nathan, Sunita, Olsson, Richard F., Verdonck, Leo F., Sharma, Akshay, Ringden, Olle, Friend, Brian D., Cerny, Jan, Choe, Hannah, Chhabra, Saurabh, Nishihori, Taiga, Seo, Sachiko, George, Biju, Baxter-Lowe, Lee Ann, Hildebrandt, Gerhard C., de Lima, Marcos, Litzow, Mark, Kebriaei, Partow, Hourigan, Christopher S., Abid, Muhammad Bilal, Weisdorf, Daniel J., Saber, Wael, Wieduwilt, Matthew J., Metheny, Leland, Zhang, Mei-Jie, Wang, Hai-Lin, Estrada-Merly, Noel, Marks, David, I, Al-Homsi, A. Samer, Muffly, Lori, Chao, Nelson, Rizzieri, David, Gale, Robert Peter, Gadalla, Shahinaz M., Cairo, Mitchell, Mussetti, Alberto, Gore, Steven, Bhatt, Vijaya Raj, Patel, Sagar S., Michelis, Fotios, V, Inamoto, Yoshihiro, Badawy, Sherif M., Copelan, Edward, Palmisiano, Neil, Kharfan-Dabaja, Mohamed A., Lazarus, Hillard M., Ganguly, Siddhartha, Bredeson, Christopher, Diaz Perez, Miguel Angel, Cassaday, Ryan, Savani, Bipin N., Ballen, Karen, Martino, Rodrigo, Wirk, Baldeep, Bacher, Ulrike, Aljurf, Mahmoud, Bashey, Asad, Murthy, Hemant S., Yared, Jean A., Aldoss, Ibrahim, Farhadfar, Nosha, Liu, Hongtao, Abdel-Azim, Hisham, Waller, Edmund K., Solh, Melhem, Seftel, Matthew D., van der Poel, Marjolein, Grunwald, Michael R., Liesveld, Jane L., Kamble, Rammurti T., McGuirk, Joseph, Munker, Reinhold, Cahn, Jean-Yves, Lee, Jong Wook, Freytes, Cesar O., Krem, Maxwell M., Winestone, Lena E., Gergis, Usama, Nathan, Sunita, Olsson, Richard F., Verdonck, Leo F., Sharma, Akshay, Ringden, Olle, Friend, Brian D., Cerny, Jan, Choe, Hannah, Chhabra, Saurabh, Nishihori, Taiga, Seo, Sachiko, George, Biju, Baxter-Lowe, Lee Ann, Hildebrandt, Gerhard C., de Lima, Marcos, Litzow, Mark, Kebriaei, Partow, Hourigan, Christopher S., Abid, Muhammad Bilal, Weisdorf, Daniel J., and Saber, Wael

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.

Published
2022
Full Text
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5. Haploidentical vs sibling, unrelated, or cord blood hematopoietic cell transplantation for acute lymphoblastic leukemia

Author

Wieduwilt, Matthew J., Metheny, Leland, Zhang, Mei-Jie, Wang, Hai-Lin, Estrada-Merly, Noel, Marks, David, I, Al-Homsi, A. Samer, Muffly, Lori, Chao, Nelson, Rizzieri, David, Gale, Robert Peter, Gadalla, Shahinaz M., Cairo, Mitchell, Mussetti, Alberto, Gore, Steven, Bhatt, Vijaya Raj, Patel, Sagar S., Michelis, Fotios, V, Inamoto, Yoshihiro, Badawy, Sherif M., Copelan, Edward, Palmisiano, Neil, Kharfan-Dabaja, Mohamed A., Lazarus, Hillard M., Ganguly, Siddhartha, Bredeson, Christopher, Diaz Perez, Miguel Angel, Cassaday, Ryan, Savani, Bipin N., Ballen, Karen, Martino, Rodrigo, Wirk, Baldeep, Bacher, Ulrike, Aljurf, Mahmoud, Bashey, Asad, Murthy, Hemant S., Yared, Jean A., Aldoss, Ibrahim, Farhadfar, Nosha, Liu, Hongtao, Abdel-Azim, Hisham, Waller, Edmund K., Solh, Melhem, Seftel, Matthew D., van der Poel, Marjolein, Grunwald, Michael R., Liesveld, Jane L., Kamble, Rammurti T., McGuirk, Joseph, Munker, Reinhold, Cahn, Jean-Yves, Lee, Jong Wook, Freytes, Cesar O., Krem, Maxwell M., Winestone, Lena E., Gergis, Usama, Nathan, Sunita, Olsson, Richard F., Verdonck, Leo F., Sharma, Akshay, Ringden, Olle, Friend, Brian D., Cerny, Jan, Choe, Hannah, Chhabra, Saurabh, Nishihori, Taiga, Seo, Sachiko, George, Biju, Baxter-Lowe, Lee Ann, Hildebrandt, Gerhard C., de Lima, Marcos, Litzow, Mark, Kebriaei, Partow, Hourigan, Christopher S., Abid, Muhammad Bilal, Weisdorf, Daniel J., Saber, Wael, Wieduwilt, Matthew J., Metheny, Leland, Zhang, Mei-Jie, Wang, Hai-Lin, Estrada-Merly, Noel, Marks, David, I, Al-Homsi, A. Samer, Muffly, Lori, Chao, Nelson, Rizzieri, David, Gale, Robert Peter, Gadalla, Shahinaz M., Cairo, Mitchell, Mussetti, Alberto, Gore, Steven, Bhatt, Vijaya Raj, Patel, Sagar S., Michelis, Fotios, V, Inamoto, Yoshihiro, Badawy, Sherif M., Copelan, Edward, Palmisiano, Neil, Kharfan-Dabaja, Mohamed A., Lazarus, Hillard M., Ganguly, Siddhartha, Bredeson, Christopher, Diaz Perez, Miguel Angel, Cassaday, Ryan, Savani, Bipin N., Ballen, Karen, Martino, Rodrigo, Wirk, Baldeep, Bacher, Ulrike, Aljurf, Mahmoud, Bashey, Asad, Murthy, Hemant S., Yared, Jean A., Aldoss, Ibrahim, Farhadfar, Nosha, Liu, Hongtao, Abdel-Azim, Hisham, Waller, Edmund K., Solh, Melhem, Seftel, Matthew D., van der Poel, Marjolein, Grunwald, Michael R., Liesveld, Jane L., Kamble, Rammurti T., McGuirk, Joseph, Munker, Reinhold, Cahn, Jean-Yves, Lee, Jong Wook, Freytes, Cesar O., Krem, Maxwell M., Winestone, Lena E., Gergis, Usama, Nathan, Sunita, Olsson, Richard F., Verdonck, Leo F., Sharma, Akshay, Ringden, Olle, Friend, Brian D., Cerny, Jan, Choe, Hannah, Chhabra, Saurabh, Nishihori, Taiga, Seo, Sachiko, George, Biju, Baxter-Lowe, Lee Ann, Hildebrandt, Gerhard C., de Lima, Marcos, Litzow, Mark, Kebriaei, Partow, Hourigan, Christopher S., Abid, Muhammad Bilal, Weisdorf, Daniel J., and Saber, Wael

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.

Published
2022
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6. Haploidentical vs sibling, unrelated, or cord blood hematopoietic cell transplantation for acute lymphoblastic leukemia

Author

Wieduwilt, Matthew J., Metheny, Leland, Zhang, Mei-Jie, Wang, Hai-Lin, Estrada-Merly, Noel, Marks, David, I, Al-Homsi, A. Samer, Muffly, Lori, Chao, Nelson, Rizzieri, David, Gale, Robert Peter, Gadalla, Shahinaz M., Cairo, Mitchell, Mussetti, Alberto, Gore, Steven, Bhatt, Vijaya Raj, Patel, Sagar S., Michelis, Fotios, V, Inamoto, Yoshihiro, Badawy, Sherif M., Copelan, Edward, Palmisiano, Neil, Kharfan-Dabaja, Mohamed A., Lazarus, Hillard M., Ganguly, Siddhartha, Bredeson, Christopher, Diaz Perez, Miguel Angel, Cassaday, Ryan, Savani, Bipin N., Ballen, Karen, Martino, Rodrigo, Wirk, Baldeep, Bacher, Ulrike, Aljurf, Mahmoud, Bashey, Asad, Murthy, Hemant S., Yared, Jean A., Aldoss, Ibrahim, Farhadfar, Nosha, Liu, Hongtao, Abdel-Azim, Hisham, Waller, Edmund K., Solh, Melhem, Seftel, Matthew D., van der Poel, Marjolein, Grunwald, Michael R., Liesveld, Jane L., Kamble, Rammurti T., McGuirk, Joseph, Munker, Reinhold, Cahn, Jean-Yves, Lee, Jong Wook, Freytes, Cesar O., Krem, Maxwell M., Winestone, Lena E., Gergis, Usama, Nathan, Sunita, Olsson, Richard F., Verdonck, Leo F., Sharma, Akshay, Ringden, Olle, Friend, Brian D., Cerny, Jan, Choe, Hannah, Chhabra, Saurabh, Nishihori, Taiga, Seo, Sachiko, George, Biju, Baxter-Lowe, Lee Ann, Hildebrandt, Gerhard C., de Lima, Marcos, Litzow, Mark, Kebriaei, Partow, Hourigan, Christopher S., Abid, Muhammad Bilal, Weisdorf, Daniel J., Saber, Wael, Wieduwilt, Matthew J., Metheny, Leland, Zhang, Mei-Jie, Wang, Hai-Lin, Estrada-Merly, Noel, Marks, David, I, Al-Homsi, A. Samer, Muffly, Lori, Chao, Nelson, Rizzieri, David, Gale, Robert Peter, Gadalla, Shahinaz M., Cairo, Mitchell, Mussetti, Alberto, Gore, Steven, Bhatt, Vijaya Raj, Patel, Sagar S., Michelis, Fotios, V, Inamoto, Yoshihiro, Badawy, Sherif M., Copelan, Edward, Palmisiano, Neil, Kharfan-Dabaja, Mohamed A., Lazarus, Hillard M., Ganguly, Siddhartha, Bredeson, Christopher, Diaz Perez, Miguel Angel, Cassaday, Ryan, Savani, Bipin N., Ballen, Karen, Martino, Rodrigo, Wirk, Baldeep, Bacher, Ulrike, Aljurf, Mahmoud, Bashey, Asad, Murthy, Hemant S., Yared, Jean A., Aldoss, Ibrahim, Farhadfar, Nosha, Liu, Hongtao, Abdel-Azim, Hisham, Waller, Edmund K., Solh, Melhem, Seftel, Matthew D., van der Poel, Marjolein, Grunwald, Michael R., Liesveld, Jane L., Kamble, Rammurti T., McGuirk, Joseph, Munker, Reinhold, Cahn, Jean-Yves, Lee, Jong Wook, Freytes, Cesar O., Krem, Maxwell M., Winestone, Lena E., Gergis, Usama, Nathan, Sunita, Olsson, Richard F., Verdonck, Leo F., Sharma, Akshay, Ringden, Olle, Friend, Brian D., Cerny, Jan, Choe, Hannah, Chhabra, Saurabh, Nishihori, Taiga, Seo, Sachiko, George, Biju, Baxter-Lowe, Lee Ann, Hildebrandt, Gerhard C., de Lima, Marcos, Litzow, Mark, Kebriaei, Partow, Hourigan, Christopher S., Abid, Muhammad Bilal, Weisdorf, Daniel J., and Saber, Wael

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.

Published
2022
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7. An adapted European LeukemiaNet genetic risk stratification for acute myeloid leukemia patients undergoing allogeneic hematopoietic cell transplant. A CIBMTR analysis

Author

Jimenez, Antonio M. Jimenez, De Lima, Marcos, Komanduri, Krishna, V, Wang, Trent P., Zhang, Mei-Jie, Chen, Karen, Abdel-Azim, Hisham, Abid, Muhammad Bilal, Aljurf, Mahmoud, Alkhateeb, Hassan, Assal, Amer, Bacher, Ulrike, Baron, Frederic, Battiwalla, Minoo, Beitinjaneh, Amer, Bejanyan, Nelli, Bhatt, Vijaya Raj, Byrne, Michael, Cahn, Jean-Yves, Cairo, Mitchell, Castillo, Paul, Copelan, Edward, DeFilipp, Zachariah, Diaz Perez, Miguel Angel, Elsawy, Mahmoud, Gale, Robert Peter, George, Biju, Grunwald, Michael R., Hildebrandt, Gerhard C., Hogan, William J., Kanakry, Christopher G., Kansagra, Ankit, Kharfan-Dabaja, Mohamed A., Khera, Nandita, Krem, Maxwell M., Lazaryan, Aleksandr, Maakaron, Joseph, Martino, Rodrigo, McGuirk, Joseph, Michelis, Fotios, V, Milone, Giuseppe, Mishra, Asmita, Murthy, Hemant S., Mussetti, Alberto, Nathan, Sunita, Nishihori, Taiga, Olsson, Richard, Palmisiano, Neil, Patel, Sagar, Saad, Ayman, Seo, Sachiko, Sharma, Akshay, Solh, Melhem, Verdonck, Leo F., Wirk, Baldeep, Yared, Jean A., Litzow, Mark, Kebriaei, Partow, Hourigan, Christopher S., Saber, Wael, Weisdorf, Daniel, Jimenez, Antonio M. Jimenez, De Lima, Marcos, Komanduri, Krishna, V, Wang, Trent P., Zhang, Mei-Jie, Chen, Karen, Abdel-Azim, Hisham, Abid, Muhammad Bilal, Aljurf, Mahmoud, Alkhateeb, Hassan, Assal, Amer, Bacher, Ulrike, Baron, Frederic, Battiwalla, Minoo, Beitinjaneh, Amer, Bejanyan, Nelli, Bhatt, Vijaya Raj, Byrne, Michael, Cahn, Jean-Yves, Cairo, Mitchell, Castillo, Paul, Copelan, Edward, DeFilipp, Zachariah, Diaz Perez, Miguel Angel, Elsawy, Mahmoud, Gale, Robert Peter, George, Biju, Grunwald, Michael R., Hildebrandt, Gerhard C., Hogan, William J., Kanakry, Christopher G., Kansagra, Ankit, Kharfan-Dabaja, Mohamed A., Khera, Nandita, Krem, Maxwell M., Lazaryan, Aleksandr, Maakaron, Joseph, Martino, Rodrigo, McGuirk, Joseph, Michelis, Fotios, V, Milone, Giuseppe, Mishra, Asmita, Murthy, Hemant S., Mussetti, Alberto, Nathan, Sunita, Nishihori, Taiga, Olsson, Richard, Palmisiano, Neil, Patel, Sagar, Saad, Ayman, Seo, Sachiko, Sharma, Akshay, Solh, Melhem, Verdonck, Leo F., Wirk, Baldeep, Yared, Jean A., Litzow, Mark, Kebriaei, Partow, Hourigan, Christopher S., Saber, Wael, and Weisdorf, Daniel

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.

Published
2021
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8. Impact of depth of clinical response on outcomes of acute myeloid leukemia patients in first complete remission who undergo allogeneic hematopoietic cell transplantation

Author

Percival, Mary-Elizabeth, Wang, Hai-Lin, Zhang, Mei-Jie, Saber, Wael, de Lima, Marcos, Litzow, Mark, Kebriaei, Partow, Abdel-Azim, Hisham, Adekola, Kehinde, Aljurf, Mahmoud, Bacher, Ulrike, Badawy, Sherif M., Beitinjaneh, Amer, Bejanyan, Nelli, Bhatt, Vijaya, Byrne, Michael, Cahn, Jean-Yves, Castillo, Paul, Chao, Nelson, Chhabra, Saurabh, Copelan, Edward, Cutler, Corey, DeFilipp, Zachariah, Dias, Ajoy, Diaz, Miguel Angel, Estey, Elihu, Farhadfar, Nosha, Frangoul, Haydar A., Freytes, Cesar O., Gale, Robert Peter, Ganguly, Siddhartha, Gowda, Lohith, Grunwald, Michael, Hossain, Nasheed, Kamble, Rammurti T., Kanakry, Christopher G., Kansagra, Ankit, Kharfan-Dabaja, Mohamed A., Krem, Maxwell, Lazarus, Hillard M., Lee, Jong Wook, Liesveld, Jane L., Lin, Richard, Liu, Hongtao, McGuirk, Joseph, Munker, Reinhold, Murthy, Hemant S., Nathan, Sunita, Nishihori, Taiga, Olsson, Richard, Palmisiano, Neil, Passweg, Jakob R., Prestidge, Tim, Ringden, Olov, Rizzieri, David A., Rybka, Witold B., Savoie, Mary Lynn, Schultz, Kirk R., Seo, Sachiko, Sharma, Akshay, Solh, Melhem, Strair, Roger, van der Poel, Marjolein, Verdonck, Leo F., Yared, Jean A., Weisdorf, Daniel, Sandmaier, Brenda M., Percival, Mary-Elizabeth, Wang, Hai-Lin, Zhang, Mei-Jie, Saber, Wael, de Lima, Marcos, Litzow, Mark, Kebriaei, Partow, Abdel-Azim, Hisham, Adekola, Kehinde, Aljurf, Mahmoud, Bacher, Ulrike, Badawy, Sherif M., Beitinjaneh, Amer, Bejanyan, Nelli, Bhatt, Vijaya, Byrne, Michael, Cahn, Jean-Yves, Castillo, Paul, Chao, Nelson, Chhabra, Saurabh, Copelan, Edward, Cutler, Corey, DeFilipp, Zachariah, Dias, Ajoy, Diaz, Miguel Angel, Estey, Elihu, Farhadfar, Nosha, Frangoul, Haydar A., Freytes, Cesar O., Gale, Robert Peter, Ganguly, Siddhartha, Gowda, Lohith, Grunwald, Michael, Hossain, Nasheed, Kamble, Rammurti T., Kanakry, Christopher G., Kansagra, Ankit, Kharfan-Dabaja, Mohamed A., Krem, Maxwell, Lazarus, Hillard M., Lee, Jong Wook, Liesveld, Jane L., Lin, Richard, Liu, Hongtao, McGuirk, Joseph, Munker, Reinhold, Murthy, Hemant S., Nathan, Sunita, Nishihori, Taiga, Olsson, Richard, Palmisiano, Neil, Passweg, Jakob R., Prestidge, Tim, Ringden, Olov, Rizzieri, David A., Rybka, Witold B., Savoie, Mary Lynn, Schultz, Kirk R., Seo, Sachiko, Sharma, Akshay, Solh, Melhem, Strair, Roger, van der Poel, Marjolein, Verdonck, Leo F., Yared, Jean A., Weisdorf, Daniel, and Sandmaier, Brenda M.

Abstract

Acute myeloid leukemia (AML) patients often undergo allogeneic hematopoietic cell transplantation (alloHCT) in first complete remission (CR). We examined the effect of depth of clinical response, including incomplete count recovery (CRi) and/or measurable residual disease (MRD), in patients from the Center for International Blood and Marrow Transplantation Research (CIBMTR) registry. We identified 2492 adult patients (1799 CR and 693 CRi) who underwent alloHCT between January 1, 2007 and December 31, 2015. The primary outcome was overall survival (OS). Multivariable analysis was performed to adjust for patient-, disease-, and transplant-related factors. Baseline characteristics were similar. Patients in CRi compared to those in CR had an increased likelihood of death (HR: 1.27; 95% confidence interval: 1.13-1.43). Compared to CR, CRi was significantly associated with increased non-relapse mortality (NRM), shorter disease-free survival (DFS), and a trend toward increased relapse. Detectable MRD was associated with shorter OS, shorter DFS, higher NRM, and increased relapse compared to absence of MRD. The deleterious effects of CRi and MRD were independent. In this large CIBMTR cohort, survival outcomes differ among AML patients based on depth of CR and presence of MRD at the time of alloHCT. Further studies should focus on optimizing post-alloHCT outcomes for patients with responses less than CR.

Published
2021
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9. Fludarabine and Melphalan Compared with Reduced Doses of Busulfan and Fludarabine Improve Transplantation Outcomes in Older Patients with Myelodysplastic Syndromes

Author

Oran, Betul, Ahn, Kwang Woo, Fretham, Caitrin, Beitinjaneh, Amer, Bashey, Asad, Pawarode, Attaphol, Wirk, Baldeep, Scott, Bart L., Savani, Bipin N., Bredeson, Christopher, Weisdorf, Daniel, Marks, David I., Rizzieri, David, Copelan, Edward, Hildebrandt, Gerhard C., Hale, Gregory A., Murthy, Hemant S., Lazarus, Hillard M., Cerny, Jan, Liesveld, Jane L., Yared, Jean A., Yves-Cahn, Jean, Szer, Jeffrey, Verdonck, Leo F., Aljurf, Mahmoud, van der Poel, Marjolein, Litzow, Mark, Kalaycio, Matt, Grunwald, Michael R., AngelDiaz, Miguel, Sabloff, Mitchell, Kharfan-Dabaja, Mohamed A., Majhail, Navneet S., Farhadfar, Nosha, Reshef, Ran, Olsson, Richard F., Gale, Robert Peter, Nakamura, Ryotaro, Seo, Sachiko, Chhabra, Saurabh, Hashmi, Shahrukh, Farhan, Shatha, Ganguly, Siddhartha, Nathan, Sunita, Nishihori, Taiga, Jain, Tania, Agrawal, Vaibhav, Bacher, Ulrike, Popat, Uday, Saber, Wael, Oran, Betul, Ahn, Kwang Woo, Fretham, Caitrin, Beitinjaneh, Amer, Bashey, Asad, Pawarode, Attaphol, Wirk, Baldeep, Scott, Bart L., Savani, Bipin N., Bredeson, Christopher, Weisdorf, Daniel, Marks, David I., Rizzieri, David, Copelan, Edward, Hildebrandt, Gerhard C., Hale, Gregory A., Murthy, Hemant S., Lazarus, Hillard M., Cerny, Jan, Liesveld, Jane L., Yared, Jean A., Yves-Cahn, Jean, Szer, Jeffrey, Verdonck, Leo F., Aljurf, Mahmoud, van der Poel, Marjolein, Litzow, Mark, Kalaycio, Matt, Grunwald, Michael R., AngelDiaz, Miguel, Sabloff, Mitchell, Kharfan-Dabaja, Mohamed A., Majhail, Navneet S., Farhadfar, Nosha, Reshef, Ran, Olsson, Richard F., Gale, Robert Peter, Nakamura, Ryotaro, Seo, Sachiko, Chhabra, Saurabh, Hashmi, Shahrukh, Farhan, Shatha, Ganguly, Siddhartha, Nathan, Sunita, Nishihori, Taiga, Jain, Tania, Agrawal, Vaibhav, Bacher, Ulrike, Popat, Uday, and Saber, Wael

Abstract

Reduced-intensity conditioning (RIC) regimens developed to extend the use of allogeneic hematopoietic stem cell transplantation (HSCT) to older patients have resulted in encouraging outcomes. We aimed to compare the 2 most commonly used RIC regimens, i.v. fludarabine with busulfan (FluBu) and fludarabine with melphalan (FluMel), in patients with myelodysplastic syndrome (MDS). Through the Center for International Blood and Marrow Transplant Research (CIBMTR), we identified 1045 MDS patients age >= 60 years who underwent first HSCT with a matched related or matched (8/8) unrelated donor using an RIC regimen. The CIBMTR's definition of RIC was used: a regimen that incorporated an i.v. busulfan total dose <= 7.2 mg/kg or a low-dose melphalan total dose <= 150 mg/m(2). The 2 groups, recipients of FluBu (n = 697) and recipients of FluMel (n = 448), were comparable in terms of disease- and transplantation-related characteristics except for the more frequent use of antithymocyte globulin or alemtuzumab in the FluBu group (39% versus 31%). The median age was 67 years in both groups. FluMel was associated with a reduced relapse incidence (RI) compared with FluBu, with a 1-year adjusted incidence of 26% versus 44% (P <=.0001). Transplantation-related mortality (TRM) was higher in the FluMel group (26% versus 16%; P <= .0001). Because the magnitude of improvement with FluMel in RI was greater than the improvement in TRM with FluBu, disease-free survival (DFS) was better at 1 year and beyond with FluMel compared with FluBu (48% versus 40% at 1 year [P =.02] and 35% versus 27% at 3 years [P =.01]). Overall survival was comparable in the 2 groups at 1 year (63% versus 61%; P =.4) but was significantly improved with FluMel compared with FluBu at 3 years (46% versus 39%; P =.03). Our results suggest that FluMel is associated with superior DFS compared with FluBu owing to reduced RI in older patients with MDS patients.

Published
2021
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10. Allogeneic Transplantation to Treat Therapy-Related Myelodysplastic Syndrome and Acute Myelogenous Leukemia in Adults

Author

Metheny, Leland, Callander, Natalie S., Hall, Aric C., Zhang, Mei-Jei, Bo-Subait, Khalid, Wang, Hai-Lin, Agrawal, Vaibhav, Samer Al-Homsi, A., Assal, Amer, Bacher, Ulrike, Beitinjaneh, Amer, Bejanyan, Nelli, Bhatt, Vijaya Raj, Bredeson, Chris, Byrne, Michael, Cairo, Mitchell, Cerny, Jan, DeFilipp, Zachariah, Diaz Perez, Miguel Angel, Freytes, César O., Ganguly, Siddhartha, Grunwald, Michael R., Hashmi, Shahrukh, Hildebrandt, Gerhard C., Inamoto, Yoshihiro, Kanakry, Christopher G., Kharfan-Dabaja, Mohamed A., Lazarus, Hillard M., Lee, Jong Wook, Nathan, Sunita, Nishihori, Taiga, Olsson, Richard F., Ringdén, Olov, Rizzieri, David, Savani, Bipin N., Savoie, Mary Lynn, Seo, Sachiko, van der Poel, Marjolein, Verdonck, Leo F., Wagner, John L., Yared, Jean A., Hourigan, Christopher S., Kebriaei, Partow, Litzow, Mark, Sandmaier, Brenda M., Saber, Wael, Weisdorf, Daniel, de Lima, Marcos, Metheny, Leland, Callander, Natalie S., Hall, Aric C., Zhang, Mei-Jei, Bo-Subait, Khalid, Wang, Hai-Lin, Agrawal, Vaibhav, Samer Al-Homsi, A., Assal, Amer, Bacher, Ulrike, Beitinjaneh, Amer, Bejanyan, Nelli, Bhatt, Vijaya Raj, Bredeson, Chris, Byrne, Michael, Cairo, Mitchell, Cerny, Jan, DeFilipp, Zachariah, Diaz Perez, Miguel Angel, Freytes, César O., Ganguly, Siddhartha, Grunwald, Michael R., Hashmi, Shahrukh, Hildebrandt, Gerhard C., Inamoto, Yoshihiro, Kanakry, Christopher G., Kharfan-Dabaja, Mohamed A., Lazarus, Hillard M., Lee, Jong Wook, Nathan, Sunita, Nishihori, Taiga, Olsson, Richard F., Ringdén, Olov, Rizzieri, David, Savani, Bipin N., Savoie, Mary Lynn, Seo, Sachiko, van der Poel, Marjolein, Verdonck, Leo F., Wagner, John L., Yared, Jean A., Hourigan, Christopher S., Kebriaei, Partow, Litzow, Mark, Sandmaier, Brenda M., Saber, Wael, Weisdorf, Daniel, and de Lima, Marcos

Abstract

Patients who develop therapy-related myeloid neoplasm, either myelodysplastic syndrome (t-MDS) or acute myelogenous leukemia (t-AML), have a poor prognosis. An earlier Center for International Blood and Marrow Transplant Research (CIBMTR) analysis of 868 allogeneic hematopoietic cell transplantations (allo-HCTs) performed between 1990 and 2004 showed a 5-year overall survival (OS) and disease-free survival (DFS) of 22% and 21%, respectively. Modern supportive care, graft-versus-host disease prophylaxis, and reduced-intensity conditioning (RIC) regimens have led to improved outcomes. Therefore, the CIBMTR analyzed 1531 allo-HCTs performed in adults with t-MDS (n = 759) or t-AML (n = 772) between and 2000 and 2014. The median age was 59 years (range, 18 to 74 years) for the patients with t-MDS and 52 years (range, 18 to 77 years) for those with tAML. Twenty-four percent of patients with t-MDS and 11% of those with t-AML had undergone a previous autologous (auto-) HCT. A myeloablative conditioning (MAC) regimen was used in 49% of patients with t-MDS and 61% of patients with t-AML. Nonrelapse mortality at 5 years was 34% (95% confidence interval [CI], 30% to 37%) for patients with t-MDS and 34% (95% CI, 30% to 37%) for those with t-AML. Relapse rates at 5 years in the 2 groups were 46% (95% CI, 43% to 50%) and 43% (95% CI, 40% to 47%). Five-year OS and DFS were 27% (95% CI, 23% to 31%) and 19% (95% CI, 16% to 23%), respectively, for patients with t-MDS and 25% (95% CI, 22% to 28%) and 23% (95% CI, 20% to 26%), respectively, for those with t-AML. In multivariate analysis, OS and DFS were significantly better in young patients with low-risk t-MDS and those with t-AML undergoing HCT with MAC while in first complete remission, but worse for those with previous auto-HCT, higher-risk cytogenetics or Revised International Prognostic Scoring System score, and a partially matched unrelated donor. Relapse remains the major cause of treatment failure, with little improvement seen

Published
2021
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11. Myeloablative Conditioning for Allogeneic Transplantation Results in Superior Disease-Free Survival for Acute Myelogenous Leukemia and Myelodysplastic Syndromes with Low/Intermediate but not High Disease Risk Index : A Center for International Blood and Marrow Transplant Research Study

Author

Bejanyan, Nelli, Zhang, Meijie, Bo-Subait, Khalid, Brunstein, Claudio, Wang, Hailin, Warlick, Erica D., Giralt, Sergio, Nishihori, Taiga, Martino, Rodrigo, Passweg, Jakob, Dias, Ajoy, Copelan, Edward, Hale, Gregory, Gale, Robert Peter, Solh, Melhem, Kharfan-Dabaja, Mohamed A., Angel Diaz, Miguel, Ganguly, Siddhartha, Gore, Steven, Verdonck, Leo F., Hossain, Nasheed M., Kekre, Natasha, Savani, Bipin, Byrne, Michael, Kanakry, Christopher, Cairo, Mitchell S., Ciurea, Stefan, Schouten, Harry C., Bredeson, Christopher, Munker, Reinhold, Lazarus, Hillard, Cahn, Jean-Yves, van der Poel, Marjolein, Rizzieri, David, Yared, Jean A., Freytes, Cesar, Cerny, Jan, Aljurf, Mahmoud, Palmisiano, Neil D., Pawarode, Attaphol, Bacher, Vera Ulrike, Grunwald, Michael R., Nathan, Sunita, Wirk, Baldeep, Hildebrandt, Gerhard C., Seo, Sachiko, Olsson, Richard, George, Biju, de Lima, Marcos, Hourigan, Christopher S., Sandmaier, Brenda M., Litzow, Mark, Kebriaei, Partow, Saber, Wael, Weisdorf, Daniel, Bejanyan, Nelli, Zhang, Meijie, Bo-Subait, Khalid, Brunstein, Claudio, Wang, Hailin, Warlick, Erica D., Giralt, Sergio, Nishihori, Taiga, Martino, Rodrigo, Passweg, Jakob, Dias, Ajoy, Copelan, Edward, Hale, Gregory, Gale, Robert Peter, Solh, Melhem, Kharfan-Dabaja, Mohamed A., Angel Diaz, Miguel, Ganguly, Siddhartha, Gore, Steven, Verdonck, Leo F., Hossain, Nasheed M., Kekre, Natasha, Savani, Bipin, Byrne, Michael, Kanakry, Christopher, Cairo, Mitchell S., Ciurea, Stefan, Schouten, Harry C., Bredeson, Christopher, Munker, Reinhold, Lazarus, Hillard, Cahn, Jean-Yves, van der Poel, Marjolein, Rizzieri, David, Yared, Jean A., Freytes, Cesar, Cerny, Jan, Aljurf, Mahmoud, Palmisiano, Neil D., Pawarode, Attaphol, Bacher, Vera Ulrike, Grunwald, Michael R., Nathan, Sunita, Wirk, Baldeep, Hildebrandt, Gerhard C., Seo, Sachiko, Olsson, Richard, George, Biju, de Lima, Marcos, Hourigan, Christopher S., Sandmaier, Brenda M., Litzow, Mark, Kebriaei, Partow, Saber, Wael, and Weisdorf, Daniel

Abstract

Compared with reduced-intensity conditioning (RIC), myeloablative conditioning (MAC) is generally associated with lower relapse risk after allogeneic hematopoietic cell transplantation (HCT) for acute myelogenous leukemia (AML) and myelodysplastic syndromes (MDS). However, disease-specific risk factors in AML/MDS can further inform when MAC and RIC may yield differential outcomes. We analyzed HCT outcomes stratified by the Disease Risk Index (DRI) in 4387 adults (age 40 to 65 years) to identify the impact of conditioning intensity. In the low/ intermediate-risk DRI cohort, RIC was associated with lower nonrelapse mortality (NRM) (hazard ratio [HR],.74; 95% confidence interval [CI],.62 to.88; P <.001) but significantly greater relapse risk (HR, 1.54; 95% CI, 1.35 to 1.76; P <.001) and thus inferior disease-free survival (DFS) (HR, 1.19; 95% CI, 1.07 to 1.33; P =.001). In the high/ very high-risk DRI cohort, RIC was associated with marginally lower NRM (HR,.83; 95% CI,.68 to 1.00; P =.051) and significantly higher relapse risk (HR, 1.23; 95% CI, 1.08 to 1.41; P =.002), leading to similar DFS using either RIC or MAC. These data support MAC over RIC as the preferred conditioning intensity for patients with AML/MDS with low/intermediate-risk DRI, but with a similar benefit as RIC in high/very high-risk DRI. Novel MAC regimens with less toxicity could benefit all patients, but more potent antineoplastic approaches are needed for the high/ very-high risk DRI group.

Published
2021
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12. Impact of type of reduced-intensity conditioning regimen on the outcomes of allogeneic haematopoietic cell transplantation in classical Hodgkin lymphoma

Author

Ahmed, Sairah, Ghosh, Nilanjan, Ahn, Kwang W., Khanal, Manoj, Litovich, Carlos, Mussetti, Alberto, Chhabra, Saurabh, Cairo, Mitchell, Mei, Matthew, William, Basem, Nathan, Sunita, Bejanyan, Nelli, Olsson, Richard, Dahi, Parastoo B., van der Poel, Marjolein, Steinberg, Amir, Kanakry, Jennifer, Cerny, Jan, Farooq, Umar, Seo, Sachiko, Kharfan-Dabaja, Mohamed A., Sureda, Anna, Fenske, Timothy S., Hamadani, Mehdi, Ahmed, Sairah, Ghosh, Nilanjan, Ahn, Kwang W., Khanal, Manoj, Litovich, Carlos, Mussetti, Alberto, Chhabra, Saurabh, Cairo, Mitchell, Mei, Matthew, William, Basem, Nathan, Sunita, Bejanyan, Nelli, Olsson, Richard, Dahi, Parastoo B., van der Poel, Marjolein, Steinberg, Amir, Kanakry, Jennifer, Cerny, Jan, Farooq, Umar, Seo, Sachiko, Kharfan-Dabaja, Mohamed A., Sureda, Anna, Fenske, Timothy S., and Hamadani, Mehdi

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).

Published
2020
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13. The Role of Donor Lymphocyte Infusion (DLI) in Post-Hematopoietic Cell Transplant (HCT) Relapse for Chronic Myeloid Leukemia (CML) in the Tyrosine Kinase Inhibitor (TKI) Era

Author

Schmidt, Sarah, Liu, Ying, Hu, Zhen-Huan, Williams, Kirsten M., Lazarus, Hillard M., Vij, Ravi, Kharfan-Dabaja, Mohamed A., Orti, Guillermo, Wiernik, Peter H., Weisdorf, Daniel, Kamble, Rammurti T., Herzig, Roger, Wirk, Baldeep, Cerny, Jan, Bacher, Ulrike, Chaudhri, Naeem A., Nathan, Sunita, Farhadfar, Nosha, Aljurf, Mahmoud, Gergis, Usama, Szer, Jeffrey, Seo, Sachiko, Hsu, Jack W., Olsson, Richard, Maharaj, Dipnarine, George, Biju, Hildebrandt, Gerhard C., Agrawal, Vaibhav, Nishihori, Taiga, Abdel-Azim, Hisham, Alyea, Edwin, Popat, Uday, Sobecks, Ronald, Scott, Bart L., Chakrabarty, Jennifer Holter, Saber, Wael, Schmidt, Sarah, Liu, Ying, Hu, Zhen-Huan, Williams, Kirsten M., Lazarus, Hillard M., Vij, Ravi, Kharfan-Dabaja, Mohamed A., Orti, Guillermo, Wiernik, Peter H., Weisdorf, Daniel, Kamble, Rammurti T., Herzig, Roger, Wirk, Baldeep, Cerny, Jan, Bacher, Ulrike, Chaudhri, Naeem A., Nathan, Sunita, Farhadfar, Nosha, Aljurf, Mahmoud, Gergis, Usama, Szer, Jeffrey, Seo, Sachiko, Hsu, Jack W., Olsson, Richard, Maharaj, Dipnarine, George, Biju, Hildebrandt, Gerhard C., Agrawal, Vaibhav, Nishihori, Taiga, Abdel-Azim, Hisham, Alyea, Edwin, Popat, Uday, Sobecks, Ronald, Scott, Bart L., Chakrabarty, Jennifer Holter, and Saber, Wael

Abstract

Treatment for relapse of chronic myeloid leukemia (CML) following hematopoietic cell transplantation (HCT) includes tyrosine kinase inhibitors (TKIs) with or without donor lymphocyte infusions (DLIs), but the most effective treatment strategy is unknown. This study was performed through the Center for International Blood and Marrow Transplant Research (CIBMTR) database. We retrospectively reviewed all patients reported to the CIBMTR registry from 2002 to 2014 who underwent HCT for CML and were alive 30 days postrelapse. A total of 215 HCT recipients relapsed and were analyzed in the following groups: (1) TKI alone (n = 128), (2) TKI with DLI (n = 48), and (3) DLI without TKI (n = 39). In multivariate analysis, disease status prior to HCT had a significant effect on overall survival (OS). Patients who received a DLI alone compared with a TKI with a DLI had inferior survival (hazard ratio, 2.28; 95% confidence interval, 1.23 to 4.24; P= .009). Those who received a TKI alone had similar survival compared with those who received a TKI with a DLI (P = .81). These data support that despite use of TKIs pretransplantation, TKI salvage therapy continues to provide significant survival following relapse in patients with CML following HCT. These data do not suggest that adding a DLI to a TKI adds an improvement in OS.

Published
2020
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14. Impact of cytogenetic abnormalities on outcomes of adult Philadelphia-negative acute lymphoblastic leukemia after allogeneic hematopoietic stem cell transplantation : a study by the Acute Leukemia Working Committee of the Center for International Blood and Marrow Transplant Research

Author

Lazaryan, Aleksandr, Dolan, Michelle, Zhang, Mei-Jie, Wang, Hai-Lin, Kharfan-Dabaja, Mohamed A., Marks, David, I, Bejanyan, Nelli, Copelan, Edward, Majhail, Navneet S., Waller, Edmund K., Chao, Nelson, Prestidge, Tim, Nishihori, Taiga, Kebriaei, Partow, Inamoto, Yoshihiro, Hamilton, Betty, Hashmi, Shahrukh K., Kamble, Rammurti T., Bacher, Ulrike, Hildebrandt, Gerhard C., Stiff, Patrick J., McGuirk, Joseph, Aldoss, Ibrahim, Beitinjaneh, Amer M., Muffly, Lori, Vij, Ravi, Olsson, Richard, Byrne, Michael, Schultz, Kirk R., Aljurf, Mahmoud, Seftel, Matthew, Savoie, Mary Lynn, Savani, Bipin N., Verdonck, Leo F., Cairo, Mitchell S., Hossain, Nasheed, Bhatt, Vijaya Raj, Frangoul, Haydar A., Abdel-Azim, Hisham, Al Malki, Monzr, Munker, Reinhold, Rizzieri, David, Khera, Nandita, Nakamura, Ryotaro, Ringden, Olle, van der Poel, Marjolein, Murthy, Hemant S., Liu, Hongtao, Mori, Shahram, De Oliveira, Satiro, Bolanos-Meade, Javier, Elsawy, Mahmoud, Barba, Pere, Nathan, Sunita, George, Biju, Pawarode, Attaphol, Grunwald, Michael, Agrawal, Vaibhav, Wang, Youjin, Assal, Amer, Caro, Paul Castillo, Kuwatsuka, Yachiyo, Seo, Sachiko, Ustun, Celalettin, Politikos, Ioannis, Lazarus, Hillard M., Saber, Wael, Sandmaier, Brenda M., De Lima, Marcos, Litzow, Mark, Bachanova, Veronika, Weisdorf, Daniel, Lazaryan, Aleksandr, Dolan, Michelle, Zhang, Mei-Jie, Wang, Hai-Lin, Kharfan-Dabaja, Mohamed A., Marks, David, I, Bejanyan, Nelli, Copelan, Edward, Majhail, Navneet S., Waller, Edmund K., Chao, Nelson, Prestidge, Tim, Nishihori, Taiga, Kebriaei, Partow, Inamoto, Yoshihiro, Hamilton, Betty, Hashmi, Shahrukh K., Kamble, Rammurti T., Bacher, Ulrike, Hildebrandt, Gerhard C., Stiff, Patrick J., McGuirk, Joseph, Aldoss, Ibrahim, Beitinjaneh, Amer M., Muffly, Lori, Vij, Ravi, Olsson, Richard, Byrne, Michael, Schultz, Kirk R., Aljurf, Mahmoud, Seftel, Matthew, Savoie, Mary Lynn, Savani, Bipin N., Verdonck, Leo F., Cairo, Mitchell S., Hossain, Nasheed, Bhatt, Vijaya Raj, Frangoul, Haydar A., Abdel-Azim, Hisham, Al Malki, Monzr, Munker, Reinhold, Rizzieri, David, Khera, Nandita, Nakamura, Ryotaro, Ringden, Olle, van der Poel, Marjolein, Murthy, Hemant S., Liu, Hongtao, Mori, Shahram, De Oliveira, Satiro, Bolanos-Meade, Javier, Elsawy, Mahmoud, Barba, Pere, Nathan, Sunita, George, Biju, Pawarode, Attaphol, Grunwald, Michael, Agrawal, Vaibhav, Wang, Youjin, Assal, Amer, Caro, Paul Castillo, Kuwatsuka, Yachiyo, Seo, Sachiko, Ustun, Celalettin, Politikos, Ioannis, Lazarus, Hillard M., Saber, Wael, Sandmaier, Brenda M., De Lima, Marcos, Litzow, Mark, Bachanova, Veronika, and Weisdorf, Daniel

Abstract

Cytogenetic risk stratification at diagnosis has long been one of the most useful tools to assess prognosis in acute lymphoblastic leukemia (ALL). To examine the prognostic impact of cytogenetic abnormalities on outcomes after allogeneic hematopoietic cell transplantation, we studied 1731 adults with Philadelphia-negative ALL in complete remission who underwent myeloablative or reduced intensity/non-myeloablative conditioning transplant from unrelated or matched sibling donors reported to the Center for International Blood and Marrow Transplant Research. A total of 632 patients had abnormal conventional metaphase cytogenetics. The leukemia-free survival and overall survival rates at 5 years after transplantation in patients with abnormal cytogenetics were 40% and 42%, respectively, which were similar to those in patients with a normal karyotype. Of the previously established cytogenetic risk classifications, modified Medical Research Council-Eastern Cooperative Oncology Group score was the only independent prognosticator of leukemia-free survival (P=0.03). In the multivariable analysis, monosomy 7 predicted post-transplant relapse [hazard ratio (HR)=2.11; 95% confidence interval (95% CI): 1.04-4.27] and treatment failure (HR=1.97; 95% CI: 1.20-3.24). Complex karyotype was prognostic for relapse (HR=1.69; 95% CI: 1.06-2.69), whereas t(8;14) predicted treatment failure (HR=2.85; 95% CI: 1.35-6.02) and overall mortality (HR=3.03; 95% CI: 1.44-6.41). This large study suggested a novel transplant-specific cytogenetic scheme with adverse [monosomy 7, complex karyotype, del(7q), t(8;14), t(11;19), del(7q), tetraploidy/near triploidy], intermediate (normal karyotype and all other abnormalities), and favorable (high hyperdiploidy) risks to prognosticate leukemia-free survival (P=0.02). Although some previously established high-risk Philadelphia-negative cytogenetic abnormalities in ALL can be overcome by transplantation, monosomy 7, complex karyotype, and t(8;14) continue to

Published
2020
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15. Impact of cytogenetic abnormalities on outcomes of adult Philadelphia-negative acute lymphoblastic leukemia after allogeneic hematopoietic stem cell transplantation : a study by the Acute Leukemia Working Committee of the Center for International Blood and Marrow Transplant Research

Author

Lazaryan, Aleksandr, Dolan, Michelle, Zhang, Mei-Jie, Wang, Hai-Lin, Kharfan-Dabaja, Mohamed A., Marks, David, I, Bejanyan, Nelli, Copelan, Edward, Majhail, Navneet S., Waller, Edmund K., Chao, Nelson, Prestidge, Tim, Nishihori, Taiga, Kebriaei, Partow, Inamoto, Yoshihiro, Hamilton, Betty, Hashmi, Shahrukh K., Kamble, Rammurti T., Bacher, Ulrike, Hildebrandt, Gerhard C., Stiff, Patrick J., McGuirk, Joseph, Aldoss, Ibrahim, Beitinjaneh, Amer M., Muffly, Lori, Vij, Ravi, Olsson, Richard, Byrne, Michael, Schultz, Kirk R., Aljurf, Mahmoud, Seftel, Matthew, Savoie, Mary Lynn, Savani, Bipin N., Verdonck, Leo F., Cairo, Mitchell S., Hossain, Nasheed, Bhatt, Vijaya Raj, Frangoul, Haydar A., Abdel-Azim, Hisham, Al Malki, Monzr, Munker, Reinhold, Rizzieri, David, Khera, Nandita, Nakamura, Ryotaro, Ringden, Olle, van der Poel, Marjolein, Murthy, Hemant S., Liu, Hongtao, Mori, Shahram, De Oliveira, Satiro, Bolanos-Meade, Javier, Elsawy, Mahmoud, Barba, Pere, Nathan, Sunita, George, Biju, Pawarode, Attaphol, Grunwald, Michael, Agrawal, Vaibhav, Wang, Youjin, Assal, Amer, Caro, Paul Castillo, Kuwatsuka, Yachiyo, Seo, Sachiko, Ustun, Celalettin, Politikos, Ioannis, Lazarus, Hillard M., Saber, Wael, Sandmaier, Brenda M., De Lima, Marcos, Litzow, Mark, Bachanova, Veronika, Weisdorf, Daniel, Lazaryan, Aleksandr, Dolan, Michelle, Zhang, Mei-Jie, Wang, Hai-Lin, Kharfan-Dabaja, Mohamed A., Marks, David, I, Bejanyan, Nelli, Copelan, Edward, Majhail, Navneet S., Waller, Edmund K., Chao, Nelson, Prestidge, Tim, Nishihori, Taiga, Kebriaei, Partow, Inamoto, Yoshihiro, Hamilton, Betty, Hashmi, Shahrukh K., Kamble, Rammurti T., Bacher, Ulrike, Hildebrandt, Gerhard C., Stiff, Patrick J., McGuirk, Joseph, Aldoss, Ibrahim, Beitinjaneh, Amer M., Muffly, Lori, Vij, Ravi, Olsson, Richard, Byrne, Michael, Schultz, Kirk R., Aljurf, Mahmoud, Seftel, Matthew, Savoie, Mary Lynn, Savani, Bipin N., Verdonck, Leo F., Cairo, Mitchell S., Hossain, Nasheed, Bhatt, Vijaya Raj, Frangoul, Haydar A., Abdel-Azim, Hisham, Al Malki, Monzr, Munker, Reinhold, Rizzieri, David, Khera, Nandita, Nakamura, Ryotaro, Ringden, Olle, van der Poel, Marjolein, Murthy, Hemant S., Liu, Hongtao, Mori, Shahram, De Oliveira, Satiro, Bolanos-Meade, Javier, Elsawy, Mahmoud, Barba, Pere, Nathan, Sunita, George, Biju, Pawarode, Attaphol, Grunwald, Michael, Agrawal, Vaibhav, Wang, Youjin, Assal, Amer, Caro, Paul Castillo, Kuwatsuka, Yachiyo, Seo, Sachiko, Ustun, Celalettin, Politikos, Ioannis, Lazarus, Hillard M., Saber, Wael, Sandmaier, Brenda M., De Lima, Marcos, Litzow, Mark, Bachanova, Veronika, and Weisdorf, Daniel

Abstract

Cytogenetic risk stratification at diagnosis has long been one of the most useful tools to assess prognosis in acute lymphoblastic leukemia (ALL). To examine the prognostic impact of cytogenetic abnormalities on outcomes after allogeneic hematopoietic cell transplantation, we studied 1731 adults with Philadelphia-negative ALL in complete remission who underwent myeloablative or reduced intensity/non-myeloablative conditioning transplant from unrelated or matched sibling donors reported to the Center for International Blood and Marrow Transplant Research. A total of 632 patients had abnormal conventional metaphase cytogenetics. The leukemia-free survival and overall survival rates at 5 years after transplantation in patients with abnormal cytogenetics were 40% and 42%, respectively, which were similar to those in patients with a normal karyotype. Of the previously established cytogenetic risk classifications, modified Medical Research Council-Eastern Cooperative Oncology Group score was the only independent prognosticator of leukemia-free survival (P=0.03). In the multivariable analysis, monosomy 7 predicted post-transplant relapse [hazard ratio (HR)=2.11; 95% confidence interval (95% CI): 1.04-4.27] and treatment failure (HR=1.97; 95% CI: 1.20-3.24). Complex karyotype was prognostic for relapse (HR=1.69; 95% CI: 1.06-2.69), whereas t(8;14) predicted treatment failure (HR=2.85; 95% CI: 1.35-6.02) and overall mortality (HR=3.03; 95% CI: 1.44-6.41). This large study suggested a novel transplant-specific cytogenetic scheme with adverse [monosomy 7, complex karyotype, del(7q), t(8;14), t(11;19), del(7q), tetraploidy/near triploidy], intermediate (normal karyotype and all other abnormalities), and favorable (high hyperdiploidy) risks to prognosticate leukemia-free survival (P=0.02). Although some previously established high-risk Philadelphia-negative cytogenetic abnormalities in ALL can be overcome by transplantation, monosomy 7, complex karyotype, and t(8;14) continue to

Published
2020
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16. Impact of cytogenetic abnormalities on outcomes of adult Philadelphia-negative acute lymphoblastic leukemia after allogeneic hematopoietic stem cell transplantation : a study by the Acute Leukemia Working Committee of the Center for International Blood and Marrow Transplant Research

Author

Lazaryan, Aleksandr, Dolan, Michelle, Zhang, Mei-Jie, Wang, Hai-Lin, Kharfan-Dabaja, Mohamed A., Marks, David, I, Bejanyan, Nelli, Copelan, Edward, Majhail, Navneet S., Waller, Edmund K., Chao, Nelson, Prestidge, Tim, Nishihori, Taiga, Kebriaei, Partow, Inamoto, Yoshihiro, Hamilton, Betty, Hashmi, Shahrukh K., Kamble, Rammurti T., Bacher, Ulrike, Hildebrandt, Gerhard C., Stiff, Patrick J., McGuirk, Joseph, Aldoss, Ibrahim, Beitinjaneh, Amer M., Muffly, Lori, Vij, Ravi, Olsson, Richard, Byrne, Michael, Schultz, Kirk R., Aljurf, Mahmoud, Seftel, Matthew, Savoie, Mary Lynn, Savani, Bipin N., Verdonck, Leo F., Cairo, Mitchell S., Hossain, Nasheed, Bhatt, Vijaya Raj, Frangoul, Haydar A., Abdel-Azim, Hisham, Al Malki, Monzr, Munker, Reinhold, Rizzieri, David, Khera, Nandita, Nakamura, Ryotaro, Ringden, Olle, van der Poel, Marjolein, Murthy, Hemant S., Liu, Hongtao, Mori, Shahram, De Oliveira, Satiro, Bolanos-Meade, Javier, Elsawy, Mahmoud, Barba, Pere, Nathan, Sunita, George, Biju, Pawarode, Attaphol, Grunwald, Michael, Agrawal, Vaibhav, Wang, Youjin, Assal, Amer, Caro, Paul Castillo, Kuwatsuka, Yachiyo, Seo, Sachiko, Ustun, Celalettin, Politikos, Ioannis, Lazarus, Hillard M., Saber, Wael, Sandmaier, Brenda M., De Lima, Marcos, Litzow, Mark, Bachanova, Veronika, Weisdorf, Daniel, Lazaryan, Aleksandr, Dolan, Michelle, Zhang, Mei-Jie, Wang, Hai-Lin, Kharfan-Dabaja, Mohamed A., Marks, David, I, Bejanyan, Nelli, Copelan, Edward, Majhail, Navneet S., Waller, Edmund K., Chao, Nelson, Prestidge, Tim, Nishihori, Taiga, Kebriaei, Partow, Inamoto, Yoshihiro, Hamilton, Betty, Hashmi, Shahrukh K., Kamble, Rammurti T., Bacher, Ulrike, Hildebrandt, Gerhard C., Stiff, Patrick J., McGuirk, Joseph, Aldoss, Ibrahim, Beitinjaneh, Amer M., Muffly, Lori, Vij, Ravi, Olsson, Richard, Byrne, Michael, Schultz, Kirk R., Aljurf, Mahmoud, Seftel, Matthew, Savoie, Mary Lynn, Savani, Bipin N., Verdonck, Leo F., Cairo, Mitchell S., Hossain, Nasheed, Bhatt, Vijaya Raj, Frangoul, Haydar A., Abdel-Azim, Hisham, Al Malki, Monzr, Munker, Reinhold, Rizzieri, David, Khera, Nandita, Nakamura, Ryotaro, Ringden, Olle, van der Poel, Marjolein, Murthy, Hemant S., Liu, Hongtao, Mori, Shahram, De Oliveira, Satiro, Bolanos-Meade, Javier, Elsawy, Mahmoud, Barba, Pere, Nathan, Sunita, George, Biju, Pawarode, Attaphol, Grunwald, Michael, Agrawal, Vaibhav, Wang, Youjin, Assal, Amer, Caro, Paul Castillo, Kuwatsuka, Yachiyo, Seo, Sachiko, Ustun, Celalettin, Politikos, Ioannis, Lazarus, Hillard M., Saber, Wael, Sandmaier, Brenda M., De Lima, Marcos, Litzow, Mark, Bachanova, Veronika, and Weisdorf, Daniel

Abstract

Cytogenetic risk stratification at diagnosis has long been one of the most useful tools to assess prognosis in acute lymphoblastic leukemia (ALL). To examine the prognostic impact of cytogenetic abnormalities on outcomes after allogeneic hematopoietic cell transplantation, we studied 1731 adults with Philadelphia-negative ALL in complete remission who underwent myeloablative or reduced intensity/non-myeloablative conditioning transplant from unrelated or matched sibling donors reported to the Center for International Blood and Marrow Transplant Research. A total of 632 patients had abnormal conventional metaphase cytogenetics. The leukemia-free survival and overall survival rates at 5 years after transplantation in patients with abnormal cytogenetics were 40% and 42%, respectively, which were similar to those in patients with a normal karyotype. Of the previously established cytogenetic risk classifications, modified Medical Research Council-Eastern Cooperative Oncology Group score was the only independent prognosticator of leukemia-free survival (P=0.03). In the multivariable analysis, monosomy 7 predicted post-transplant relapse [hazard ratio (HR)=2.11; 95% confidence interval (95% CI): 1.04-4.27] and treatment failure (HR=1.97; 95% CI: 1.20-3.24). Complex karyotype was prognostic for relapse (HR=1.69; 95% CI: 1.06-2.69), whereas t(8;14) predicted treatment failure (HR=2.85; 95% CI: 1.35-6.02) and overall mortality (HR=3.03; 95% CI: 1.44-6.41). This large study suggested a novel transplant-specific cytogenetic scheme with adverse [monosomy 7, complex karyotype, del(7q), t(8;14), t(11;19), del(7q), tetraploidy/near triploidy], intermediate (normal karyotype and all other abnormalities), and favorable (high hyperdiploidy) risks to prognosticate leukemia-free survival (P=0.02). Although some previously established high-risk Philadelphia-negative cytogenetic abnormalities in ALL can be overcome by transplantation, monosomy 7, complex karyotype, and t(8;14) continue to

Published
2020
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17. Impact of cytogenetic abnormalities on outcomes of adult Philadelphia-negative acute lymphoblastic leukemia after allogeneic hematopoietic stem cell transplantation : a study by the Acute Leukemia Working Committee of the Center for International Blood and Marrow Transplant Research

Author

Lazaryan, Aleksandr, Dolan, Michelle, Zhang, Mei-Jie, Wang, Hai-Lin, Kharfan-Dabaja, Mohamed A., Marks, David, I, Bejanyan, Nelli, Copelan, Edward, Majhail, Navneet S., Waller, Edmund K., Chao, Nelson, Prestidge, Tim, Nishihori, Taiga, Kebriaei, Partow, Inamoto, Yoshihiro, Hamilton, Betty, Hashmi, Shahrukh K., Kamble, Rammurti T., Bacher, Ulrike, Hildebrandt, Gerhard C., Stiff, Patrick J., McGuirk, Joseph, Aldoss, Ibrahim, Beitinjaneh, Amer M., Muffly, Lori, Vij, Ravi, Olsson, Richard, Byrne, Michael, Schultz, Kirk R., Aljurf, Mahmoud, Seftel, Matthew, Savoie, Mary Lynn, Savani, Bipin N., Verdonck, Leo F., Cairo, Mitchell S., Hossain, Nasheed, Bhatt, Vijaya Raj, Frangoul, Haydar A., Abdel-Azim, Hisham, Al Malki, Monzr, Munker, Reinhold, Rizzieri, David, Khera, Nandita, Nakamura, Ryotaro, Ringden, Olle, van der Poel, Marjolein, Murthy, Hemant S., Liu, Hongtao, Mori, Shahram, De Oliveira, Satiro, Bolanos-Meade, Javier, Elsawy, Mahmoud, Barba, Pere, Nathan, Sunita, George, Biju, Pawarode, Attaphol, Grunwald, Michael, Agrawal, Vaibhav, Wang, Youjin, Assal, Amer, Caro, Paul Castillo, Kuwatsuka, Yachiyo, Seo, Sachiko, Ustun, Celalettin, Politikos, Ioannis, Lazarus, Hillard M., Saber, Wael, Sandmaier, Brenda M., De Lima, Marcos, Litzow, Mark, Bachanova, Veronika, Weisdorf, Daniel, Lazaryan, Aleksandr, Dolan, Michelle, Zhang, Mei-Jie, Wang, Hai-Lin, Kharfan-Dabaja, Mohamed A., Marks, David, I, Bejanyan, Nelli, Copelan, Edward, Majhail, Navneet S., Waller, Edmund K., Chao, Nelson, Prestidge, Tim, Nishihori, Taiga, Kebriaei, Partow, Inamoto, Yoshihiro, Hamilton, Betty, Hashmi, Shahrukh K., Kamble, Rammurti T., Bacher, Ulrike, Hildebrandt, Gerhard C., Stiff, Patrick J., McGuirk, Joseph, Aldoss, Ibrahim, Beitinjaneh, Amer M., Muffly, Lori, Vij, Ravi, Olsson, Richard, Byrne, Michael, Schultz, Kirk R., Aljurf, Mahmoud, Seftel, Matthew, Savoie, Mary Lynn, Savani, Bipin N., Verdonck, Leo F., Cairo, Mitchell S., Hossain, Nasheed, Bhatt, Vijaya Raj, Frangoul, Haydar A., Abdel-Azim, Hisham, Al Malki, Monzr, Munker, Reinhold, Rizzieri, David, Khera, Nandita, Nakamura, Ryotaro, Ringden, Olle, van der Poel, Marjolein, Murthy, Hemant S., Liu, Hongtao, Mori, Shahram, De Oliveira, Satiro, Bolanos-Meade, Javier, Elsawy, Mahmoud, Barba, Pere, Nathan, Sunita, George, Biju, Pawarode, Attaphol, Grunwald, Michael, Agrawal, Vaibhav, Wang, Youjin, Assal, Amer, Caro, Paul Castillo, Kuwatsuka, Yachiyo, Seo, Sachiko, Ustun, Celalettin, Politikos, Ioannis, Lazarus, Hillard M., Saber, Wael, Sandmaier, Brenda M., De Lima, Marcos, Litzow, Mark, Bachanova, Veronika, and Weisdorf, Daniel

Abstract

Cytogenetic risk stratification at diagnosis has long been one of the most useful tools to assess prognosis in acute lymphoblastic leukemia (ALL). To examine the prognostic impact of cytogenetic abnormalities on outcomes after allogeneic hematopoietic cell transplantation, we studied 1731 adults with Philadelphia-negative ALL in complete remission who underwent myeloablative or reduced intensity/non-myeloablative conditioning transplant from unrelated or matched sibling donors reported to the Center for International Blood and Marrow Transplant Research. A total of 632 patients had abnormal conventional metaphase cytogenetics. The leukemia-free survival and overall survival rates at 5 years after transplantation in patients with abnormal cytogenetics were 40% and 42%, respectively, which were similar to those in patients with a normal karyotype. Of the previously established cytogenetic risk classifications, modified Medical Research Council-Eastern Cooperative Oncology Group score was the only independent prognosticator of leukemia-free survival (P=0.03). In the multivariable analysis, monosomy 7 predicted post-transplant relapse [hazard ratio (HR)=2.11; 95% confidence interval (95% CI): 1.04-4.27] and treatment failure (HR=1.97; 95% CI: 1.20-3.24). Complex karyotype was prognostic for relapse (HR=1.69; 95% CI: 1.06-2.69), whereas t(8;14) predicted treatment failure (HR=2.85; 95% CI: 1.35-6.02) and overall mortality (HR=3.03; 95% CI: 1.44-6.41). This large study suggested a novel transplant-specific cytogenetic scheme with adverse [monosomy 7, complex karyotype, del(7q), t(8;14), t(11;19), del(7q), tetraploidy/near triploidy], intermediate (normal karyotype and all other abnormalities), and favorable (high hyperdiploidy) risks to prognosticate leukemia-free survival (P=0.02). Although some previously established high-risk Philadelphia-negative cytogenetic abnormalities in ALL can be overcome by transplantation, monosomy 7, complex karyotype, and t(8;14) continue to

Published
2020
Full Text
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18. Impact of cytogenetic abnormalities on outcomes of adult Philadelphia-negative acute lymphoblastic leukemia after allogeneic hematopoietic stem cell transplantation : a study by the Acute Leukemia Working Committee of the Center for International Blood and Marrow Transplant Research

Author

Lazaryan, Aleksandr, Dolan, Michelle, Zhang, Mei-Jie, Wang, Hai-Lin, Kharfan-Dabaja, Mohamed A., Marks, David, I, Bejanyan, Nelli, Copelan, Edward, Majhail, Navneet S., Waller, Edmund K., Chao, Nelson, Prestidge, Tim, Nishihori, Taiga, Kebriaei, Partow, Inamoto, Yoshihiro, Hamilton, Betty, Hashmi, Shahrukh K., Kamble, Rammurti T., Bacher, Ulrike, Hildebrandt, Gerhard C., Stiff, Patrick J., McGuirk, Joseph, Aldoss, Ibrahim, Beitinjaneh, Amer M., Muffly, Lori, Vij, Ravi, Olsson, Richard, Byrne, Michael, Schultz, Kirk R., Aljurf, Mahmoud, Seftel, Matthew, Savoie, Mary Lynn, Savani, Bipin N., Verdonck, Leo F., Cairo, Mitchell S., Hossain, Nasheed, Bhatt, Vijaya Raj, Frangoul, Haydar A., Abdel-Azim, Hisham, Al Malki, Monzr, Munker, Reinhold, Rizzieri, David, Khera, Nandita, Nakamura, Ryotaro, Ringden, Olle, van der Poel, Marjolein, Murthy, Hemant S., Liu, Hongtao, Mori, Shahram, De Oliveira, Satiro, Bolanos-Meade, Javier, Elsawy, Mahmoud, Barba, Pere, Nathan, Sunita, George, Biju, Pawarode, Attaphol, Grunwald, Michael, Agrawal, Vaibhav, Wang, Youjin, Assal, Amer, Caro, Paul Castillo, Kuwatsuka, Yachiyo, Seo, Sachiko, Ustun, Celalettin, Politikos, Ioannis, Lazarus, Hillard M., Saber, Wael, Sandmaier, Brenda M., De Lima, Marcos, Litzow, Mark, Bachanova, Veronika, Weisdorf, Daniel, Lazaryan, Aleksandr, Dolan, Michelle, Zhang, Mei-Jie, Wang, Hai-Lin, Kharfan-Dabaja, Mohamed A., Marks, David, I, Bejanyan, Nelli, Copelan, Edward, Majhail, Navneet S., Waller, Edmund K., Chao, Nelson, Prestidge, Tim, Nishihori, Taiga, Kebriaei, Partow, Inamoto, Yoshihiro, Hamilton, Betty, Hashmi, Shahrukh K., Kamble, Rammurti T., Bacher, Ulrike, Hildebrandt, Gerhard C., Stiff, Patrick J., McGuirk, Joseph, Aldoss, Ibrahim, Beitinjaneh, Amer M., Muffly, Lori, Vij, Ravi, Olsson, Richard, Byrne, Michael, Schultz, Kirk R., Aljurf, Mahmoud, Seftel, Matthew, Savoie, Mary Lynn, Savani, Bipin N., Verdonck, Leo F., Cairo, Mitchell S., Hossain, Nasheed, Bhatt, Vijaya Raj, Frangoul, Haydar A., Abdel-Azim, Hisham, Al Malki, Monzr, Munker, Reinhold, Rizzieri, David, Khera, Nandita, Nakamura, Ryotaro, Ringden, Olle, van der Poel, Marjolein, Murthy, Hemant S., Liu, Hongtao, Mori, Shahram, De Oliveira, Satiro, Bolanos-Meade, Javier, Elsawy, Mahmoud, Barba, Pere, Nathan, Sunita, George, Biju, Pawarode, Attaphol, Grunwald, Michael, Agrawal, Vaibhav, Wang, Youjin, Assal, Amer, Caro, Paul Castillo, Kuwatsuka, Yachiyo, Seo, Sachiko, Ustun, Celalettin, Politikos, Ioannis, Lazarus, Hillard M., Saber, Wael, Sandmaier, Brenda M., De Lima, Marcos, Litzow, Mark, Bachanova, Veronika, and Weisdorf, Daniel

Abstract

Cytogenetic risk stratification at diagnosis has long been one of the most useful tools to assess prognosis in acute lymphoblastic leukemia (ALL). To examine the prognostic impact of cytogenetic abnormalities on outcomes after allogeneic hematopoietic cell transplantation, we studied 1731 adults with Philadelphia-negative ALL in complete remission who underwent myeloablative or reduced intensity/non-myeloablative conditioning transplant from unrelated or matched sibling donors reported to the Center for International Blood and Marrow Transplant Research. A total of 632 patients had abnormal conventional metaphase cytogenetics. The leukemia-free survival and overall survival rates at 5 years after transplantation in patients with abnormal cytogenetics were 40% and 42%, respectively, which were similar to those in patients with a normal karyotype. Of the previously established cytogenetic risk classifications, modified Medical Research Council-Eastern Cooperative Oncology Group score was the only independent prognosticator of leukemia-free survival (P=0.03). In the multivariable analysis, monosomy 7 predicted post-transplant relapse [hazard ratio (HR)=2.11; 95% confidence interval (95% CI): 1.04-4.27] and treatment failure (HR=1.97; 95% CI: 1.20-3.24). Complex karyotype was prognostic for relapse (HR=1.69; 95% CI: 1.06-2.69), whereas t(8;14) predicted treatment failure (HR=2.85; 95% CI: 1.35-6.02) and overall mortality (HR=3.03; 95% CI: 1.44-6.41). This large study suggested a novel transplant-specific cytogenetic scheme with adverse [monosomy 7, complex karyotype, del(7q), t(8;14), t(11;19), del(7q), tetraploidy/near triploidy], intermediate (normal karyotype and all other abnormalities), and favorable (high hyperdiploidy) risks to prognosticate leukemia-free survival (P=0.02). Although some previously established high-risk Philadelphia-negative cytogenetic abnormalities in ALL can be overcome by transplantation, monosomy 7, complex karyotype, and t(8;14) continue to

Published
2020
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