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2. Landscape of genetic lesions in 944 patients with myelodysplastic syndromes

Author

Haferlach, T, Nagata, Y, Grossmann, V, Okuno, Y, Bacher, U, Nagae, G, Schnittger, S, Sanada, M, Kon, A, Alpermann, T, Yoshida, K, Roller, A, Nadarajah, N, Shiraishi, Y, Shiozawa, Y, Chiba, K, Tanaka, H, Koeffler, HP, Klein, H-U, Dugas, M, Aburatani, H, Kohlmann, A, Miyano, S, Haferlach, C, Kern, W, and Ogawa, S

Subjects
Genetic Testing, Clinical Research, Rare Diseases, Human Genome, Genetics, Biotechnology, Cancer, Hematology, Adult, Aged, Aged, 80 and over, Female, Gene Frequency, Genetic Association Studies, Genetic Markers, High-Throughput Nucleotide Sequencing, Humans, Male, Middle Aged, Mutation, Mutation Rate, Myelodysplastic Syndromes, Polymorphism, Single Nucleotide, Prognosis, Proportional Hazards Models, Young Adult, next-generation sequencing, molecular markers, myelodysplastic syndromes, prognostic score, Clinical Sciences, Oncology and Carcinogenesis, Immunology
Abstract

High-throughput DNA sequencing significantly contributed to diagnosis and prognostication in patients with myelodysplastic syndromes (MDS). We determined the biological and prognostic significance of genetic aberrations in MDS. In total, 944 patients with various MDS subtypes were screened for known/putative mutations/deletions in 104 genes using targeted deep sequencing and array-based genomic hybridization. In total, 845/944 patients (89.5%) harbored at least one mutation (median, 3 per patient; range, 0-12). Forty-seven genes were significantly mutated with TET2, SF3B1, ASXL1, SRSF2, DNMT3A, and RUNX1 mutated in >10% of cases. Many mutations were associated with higher risk groups and/or blast elevation. Survival was investigated in 875 patients. By univariate analysis, 25/48 genes (resulting from 47 genes tested significantly plus PRPF8) affected survival (P

Published
2014

4. Long-term survival outcomes of reduced-intensity allogeneic or autologous transplantation in relapsed grade 3 follicular lymphoma

Author

Klyuchnikov, E, Bacher, U, Woo Ahn, K, Carreras, J, Kröger, N M, Hari, P N, Ku, G H, Ayala, E, Chen, A I, Chen, Y-B, Cohen, J B, Freytes, C O, Gale, R P, Kamble, R T, Kharfan-Dabaja, M A, Lazarus, H M, Martino, R, Mussetti, A, Savani, B N, Schouten, H C, Usmani, S Z, Wiernik, P H, Wirk, B, Smith, S M, Sureda, A, and Hamadani, M

Published
2016
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10. Alternative donors extend transplantation for patients with lymphoma who lack an HLA matched donor

Author

Bachanova, V, Burns, L J, Wang, T, Carreras, J, Gale, R P, Wiernik, P H, Ballen, K K, Wirk, B, Munker, R, Rizzieri, D A, Chen, Y-B, Gibson, J, Akpek, G, Costa, L J, Kamble, R T, Aljurf, M D, Hsu, J W, Cairo, M S, Schouten, H C, Bacher, U, Savani, B N, Wingard, J R, Lazarus, H M, Laport, G G, Montoto, S, Maloney, D G, Smith, S M, Brunstein, C, and Saber, W

Published
2015
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13. Ph+ ALL patients in first complete remission have similar survival after reduced intensity and myeloablative allogeneic transplantation: impact of tyrosine kinase inhibitor and minimal residual disease

Author

Bachanova, V, Marks, D I, Zhang, M-J, Wang, H, de Lima, M, Aljurf, M D, Arellano, M, Artz, A S, Bacher, U, Cahn, J-Y, Chen, Y-B, Copelan, E A, Drobyski, W R, Gale, R P, Greer, J P, Gupta, V, Hale, G A, Kebriaei, P, Lazarus, H M, Lewis, I D, Lewis, V A, Liesveld, J L, Litzow, M R, Loren, A W, Miller, A M, Norkin, M, Oran, B, Pidala, J, Rowe, J M, Savani, B N, Saber, W, Vij, R, Waller, E K, Wiernik, P H, and Weisdorf, D J

Published
2014
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27. Fludarabine and Melphalan Compared with Reduced Doses of Busulfan and Fludarabine Improve Transplantation Outcomes in Older Patients with Myelodysplastic Syndromes

Author

Oran, B, Ahn, KW, Fretham, C, Beitinjaneh, A, Bashey, A, Pawarode, A, Wirk, B, Scott, BL, Savani, BN, Bredeson, C, Weisdorf, D, Marks, DI, Rizzieri, D, Copelan, E, Hildebrandt, GC, Hale, GA, Murthy, HS, Lazarus, HM, Cerny, J, Liesveld, JL, Yared, JA, Yves-Cahn, J, Szer, J, Verdonck, LF, MahmoudAljurf, van der Poel, M, Litzow, M, Kalaycio, M, Grunwald, MR, AngelDiaz, M, Sabloff, M, Kharfan-Dabaja, MA, Majhail, NS, Farhadfar, N, Reshef, R, Olsson, RF, Gale, RP, Nakamura, R, Seo, S, Chhabra, S, Hashmi, S, Farhan, S, Ganguly, S, Nathan, S, TaigaNishihori, Jain, T, VaibhavAgrawal, Bacher, U, Popat, U, Saber, W, Oran, B, Ahn, KW, Fretham, C, Beitinjaneh, A, Bashey, A, Pawarode, A, Wirk, B, Scott, BL, Savani, BN, Bredeson, C, Weisdorf, D, Marks, DI, Rizzieri, D, Copelan, E, Hildebrandt, GC, Hale, GA, Murthy, HS, Lazarus, HM, Cerny, J, Liesveld, JL, Yared, JA, Yves-Cahn, J, Szer, J, Verdonck, LF, MahmoudAljurf, van der Poel, M, Litzow, M, Kalaycio, M, Grunwald, MR, AngelDiaz, M, Sabloff, M, Kharfan-Dabaja, MA, Majhail, NS, Farhadfar, N, Reshef, R, Olsson, RF, Gale, RP, Nakamura, R, Seo, S, Chhabra, S, Hashmi, S, Farhan, S, Ganguly, S, Nathan, S, TaigaNishihori, Jain, T, VaibhavAgrawal, Bacher, U, Popat, U, and Saber, W

Published
2021

46. Comparison of outcomes of HCT in blast phase of BCR-ABL1(-) MPN with de novo AML and with AML following MDS

Author

Gupta, V, Kim, S, Hu, Z-H, Liu, Y, Aljurf, M, Bacher, U, Beitinjaneh, A, Cahn, J-Y, Cerny, J, Copelan, E, Gadalla, SM, Gale, RP, Ganguly, S, George, B, Gerds, AT, Gergis, U, Hamilton, BK, Hashmi, S, Hildebrandt, GC, Kamble, RT, Kindwall-Keller, T, Lazarus, HM, Liesveld, JL, Litzow, M, Maziarz, RT, Nishihori, T, Olsson, RF, Rizzieri, D, Savani, BN, Seo, S, Solh, M, Szer, J, Verdonck, LF, Wirk, B, Woolfrey, A, Yared, JA, Alyea, EP, Popat, UR, Sobecks, RM, Scott, BL, Nakamura, R, Saber, W, Gupta, V, Kim, S, Hu, Z-H, Liu, Y, Aljurf, M, Bacher, U, Beitinjaneh, A, Cahn, J-Y, Cerny, J, Copelan, E, Gadalla, SM, Gale, RP, Ganguly, S, George, B, Gerds, AT, Gergis, U, Hamilton, BK, Hashmi, S, Hildebrandt, GC, Kamble, RT, Kindwall-Keller, T, Lazarus, HM, Liesveld, JL, Litzow, M, Maziarz, RT, Nishihori, T, Olsson, RF, Rizzieri, D, Savani, BN, Seo, S, Solh, M, Szer, J, Verdonck, LF, Wirk, B, Woolfrey, A, Yared, JA, Alyea, EP, Popat, UR, Sobecks, RM, Scott, BL, Nakamura, R, and Saber, W

Abstract

Comparative outcomes of allogeneic hematopoietic cell transplantation (HCT) for BCR-ABL1- myeloproliferative neoplasms (MPNs) in blast phase (MPN-BP) vs de novo acute myeloid leukemia (AML), and AML with prior myelodysplastic syndromes (MDSs; post-MDS AML), are unknown. Using the Center for International Blood and Marrow Transplant Research (CIBMTR) database, we compared HCT outcomes in 177 MPN-BP patients with 4749 patients with de novo AML, and 1104 patients with post-MDS AML, using multivariate regression analysis in 2 separate comparisons. In a multivariate Cox model, no difference in overall survival (OS) or relapse was observed in patients with MPN-BP vs de novo AML with active leukemia at HCT. Patients with MPN-BP in remission had inferior OS in comparison with de novo AML in remission (hazard ratio [HR], 1.40 [95% confidence interval [CI], 1.12-1.76]) due to higher relapse rate (HR, 2.18 [95% CI, 1.69-2.80]). MPN-BP patients had inferior OS (HR, 1.19 [95% CI, 1.00-1.43]) and increased relapse (HR, 1.60 [95% CI, 1.31-1.96]) compared with post-MDS AML. Poor-risk cytogenetics were associated with increased relapse in both comparisons. Peripheral blood grafts were associated with decreased relapse in MPN-BP and post-MDS AML (HR, 0.70 [95% CI, 0.57-0.86]). Nonrelapse mortality (NRM) was similar between MPN-BP vs de novo AML, and MPN-BP vs post-MDS AML. Total-body irradiation-based myeloablative conditioning was associated with higher NRM in both comparisons. Survival of MPN-BP after HCT is inferior to de novo AML in remission and post-MDS AML due to increased relapse. Relapse-prevention strategies are required to optimize HCT outcomes in MPN-BP.

Published
2020

47. Maintenance Tyrosine Kinase Inhibitors Following Allogeneic Hematopoietic Stem Cell Transplantation for Chronic Myelogenous Leukemia: A Center for International Blood and Marrow Transplant Research Study

Author

DeFilipp, Z, Ancheta, R, Liu, Y, Hu, Z-H, Gale, RP, Snyder, D, Schouten, HC, Kalaycio, M, Hildebrandt, GC, Ustun, C, Daly, A, Ganguly, S, Inamoto, Y, Litzow, M, Szer, J, Savoie, ML, Hossain, N, Kharfan-Dabaja, MA, Hamadani, M, Reshef, R, Bajel, A, Schultz, KR, Gadalla, S, Gerds, A, Liesveld, J, Juckett, MB, Kamble, R, Hashmi, S, Abdel-Azim, H, Solh, M, Bacher, U, Lazarus, H, Olsson, R, Cahn, J-Y, Grunwald, MR, Savani, BN, Yared, J, Rowe, JM, Cerny, J, Chaudhri, NA, Aljurf, M, Beitinjaneh, A, Seo, S, Nishihori, T, Hsu, JW, Ramanathan, M, Alyea, E, Popat, U, Sobecks, R, Saber, W, DeFilipp, Z, Ancheta, R, Liu, Y, Hu, Z-H, Gale, RP, Snyder, D, Schouten, HC, Kalaycio, M, Hildebrandt, GC, Ustun, C, Daly, A, Ganguly, S, Inamoto, Y, Litzow, M, Szer, J, Savoie, ML, Hossain, N, Kharfan-Dabaja, MA, Hamadani, M, Reshef, R, Bajel, A, Schultz, KR, Gadalla, S, Gerds, A, Liesveld, J, Juckett, MB, Kamble, R, Hashmi, S, Abdel-Azim, H, Solh, M, Bacher, U, Lazarus, H, Olsson, R, Cahn, J-Y, Grunwald, MR, Savani, BN, Yared, J, Rowe, JM, Cerny, J, Chaudhri, NA, Aljurf, M, Beitinjaneh, A, Seo, S, Nishihori, T, Hsu, JW, Ramanathan, M, Alyea, E, Popat, U, Sobecks, R, and Saber, W

Abstract

It remains unknown whether the administration of tyrosine kinase inhibitors (TKIs) targeting BCR-ABL1 after allogeneic hematopoietic cell transplantation (HCT) is associated with improved outcomes for patients with chronic myelogenous leukemia (CML). In this registry study, we analyzed clinical outcomes of 390 adult patients with CML who underwent transplantation between 2007 and 2014 and received maintenance TKI following HCT (n = 89) compared with no TKI maintenance (n = 301), as reported to the Center for International Blood and Marrow Transplant Research. All patients received TKI therapy before HCT. The majority of patients had a disease status of first chronic phase at HCT (n = 240; 62%). The study was conducted as a landmark analysis, excluding patients who died, relapsed, had chronic graft-versus-host disease, or were censored before day +100 following HCT. Of the 89 patients who received TKI maintenance, 77 (87%) received a single TKI and the other 12 (13%) received multiple sequential TKIs. The most common TKIs used for maintenance were dasatinib (n = 50), imatinib (n = 27), and nilotinib (n = 27). As measured from day +100, the adjusted estimates for 5-year relapse (maintenance, 35% versus no maintenance, 26%; P = .11), leukemia-free survival (maintenance, 42% versus no maintenance, 44%; P = .65), or overall survival (maintenance, 61% versus no maintenance, 57%; P = .61) did not differ significantly between patients receiving TKI maintenance or no maintenance. These results remained unchanged in multivariate analysis and were not modified by disease status before transplantation. In conclusion, our data from this day +100 landmark analysis do not demonstrate a significant impact of maintenance TKI therapy on clinical outcomes. The optimal approach to TKI administration in the post-transplantation setting in patients with CML remains undetermined.

Published
2020

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