Reduced intensity conditioned allograft yields favorable survival for older adults with B-cell acute lymphoblastic leukemia

Ashley E. Rosko, Hai Lin Wang, Marcos de Lima, Brenda Sandmaier, H. Jean Khoury, Andrew Artz, Johnathan Brammer, Christopher Bredeson, Sherif Farag, Mohamed Kharfan-Dabaja, Hillard M. Lazarus, David I. Marks, Rodrigo Martino Bufarull, Joseph McGuirk, Mohamed Mohty, Taiga Nishihori, Ian Nivison-Smith, Armin Rashidi, Olle Ringden, Matthew Seftel & 3 others Daniel Weisdorf, Veronika Bachanova, Wael Saber

Research output: Contribution to journalArticle

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Abstract

Older adults with B-cell acute lymphoblastic leukemia (B-ALL) have poor survival. We examined the effectiveness of reduced intensity conditioning (RIC) hematopoietic cell transplant (HCT) in adults with B-ALL age 55 years and older and explored prognostic factors associated with long-term outcomes. Using CIBMTR registry data, we evaluated 273 patients (median age 61, range 55–72) with B-ALL with disease status in CR1 (71%), >CR2 (17%) and Primary Induction Failure (PIF)/Relapse (11%), who underwent RIC HCT between 2001 and 2012 using mostly unrelated donor (59%) or HLA-matched sibling (32%). Among patients with available cytogenetic data, the Philadelphia chromosome (Ph+) was present in 50%. The 3-year cumulative incidences of nonrelapse mortality (NRM) and relapse were 25% (95% confidence intervals (CI): 20–31%) and 47% (95% CI: 41–53%), respectively. Three-year overall survival (OS) was 38% (95% CI: 33–44%). Relapse remained the leading cause of death accounting for 49% of all deaths. In univariate analysis, 3 year risk of NRM was significantly higher with reduced Karnofsky performance status (KPS <90: 34% (95% CI: 25–43%) versus KPS ≥90 (18%; 95% CI: 12–24%, P = 0.006). Mortality was increased in older adults (66+ vs. 55–60: Relative Risk [RR] 1.51 95% CI: 1.00–2.29, P = 0.05) and those with advanced disease (RR 2.13; 95% CI: 1.36–3.34, P = 0.001). Survival of patients in CR1 yields 45% (95% CI: 38–52%) at 3 years and no relapse occurred after 2 years. We report promising OS and acceptable NRM using RIC HCT in older patients with B-ALL. Disease status in CR1 and good performance status are associated with improved outcomes. Am. J. Hematol. 92:42–49, 2017.

Original languageEnglish (US)
Pages (from-to)42-49
Number of pages8
JournalAmerican Journal of Hematology
Volume92
Issue number1
DOIs
StatePublished - Jan 1 2017

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Precursor Cell Lymphoblastic Leukemia-Lymphoma
Allografts
B-Lymphocytes
Confidence Intervals
Survival
Recurrence
Mortality
Transplants
Karnofsky Performance Status
Philadelphia Chromosome
Unrelated Donors
Cytogenetics
Registries
Siblings
Cause of Death
Incidence
Conditioning (Psychology)

ASJC Scopus subject areas

  • Hematology

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Reduced intensity conditioned allograft yields favorable survival for older adults with B-cell acute lymphoblastic leukemia. / Rosko, Ashley E.; Wang, Hai Lin; de Lima, Marcos; Sandmaier, Brenda; Khoury, H. Jean; Artz, Andrew; Brammer, Johnathan; Bredeson, Christopher; Farag, Sherif; Kharfan-Dabaja, Mohamed; Lazarus, Hillard M.; Marks, David I.; Martino Bufarull, Rodrigo; McGuirk, Joseph; Mohty, Mohamed; Nishihori, Taiga; Nivison-Smith, Ian; Rashidi, Armin; Ringden, Olle; Seftel, Matthew; Weisdorf, Daniel; Bachanova, Veronika; Saber, Wael.

In: American Journal of Hematology, Vol. 92, No. 1, 01.01.2017, p. 42-49.

Research output: Contribution to journalArticle

Rosko, AE, Wang, HL, de Lima, M, Sandmaier, B, Khoury, HJ, Artz, A, Brammer, J, Bredeson, C, Farag, S, Kharfan-Dabaja, M, Lazarus, HM, Marks, DI, Martino Bufarull, R, McGuirk, J, Mohty, M, Nishihori, T, Nivison-Smith, I, Rashidi, A, Ringden, O, Seftel, M, Weisdorf, D, Bachanova, V & Saber, W 2017, 'Reduced intensity conditioned allograft yields favorable survival for older adults with B-cell acute lymphoblastic leukemia', American Journal of Hematology, vol. 92, no. 1, pp. 42-49. https://doi.org/10.1002/ajh.24575
Rosko, Ashley E. ; Wang, Hai Lin ; de Lima, Marcos ; Sandmaier, Brenda ; Khoury, H. Jean ; Artz, Andrew ; Brammer, Johnathan ; Bredeson, Christopher ; Farag, Sherif ; Kharfan-Dabaja, Mohamed ; Lazarus, Hillard M. ; Marks, David I. ; Martino Bufarull, Rodrigo ; McGuirk, Joseph ; Mohty, Mohamed ; Nishihori, Taiga ; Nivison-Smith, Ian ; Rashidi, Armin ; Ringden, Olle ; Seftel, Matthew ; Weisdorf, Daniel ; Bachanova, Veronika ; Saber, Wael. / Reduced intensity conditioned allograft yields favorable survival for older adults with B-cell acute lymphoblastic leukemia. In: American Journal of Hematology. 2017 ; Vol. 92, No. 1. pp. 42-49.
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AU - Rosko, Ashley E.

AU - Wang, Hai Lin

AU - de Lima, Marcos

AU - Sandmaier, Brenda

AU - Khoury, H. Jean

AU - Artz, Andrew

AU - Brammer, Johnathan

AU - Bredeson, Christopher

AU - Farag, Sherif

AU - Kharfan-Dabaja, Mohamed

AU - Lazarus, Hillard M.

AU - Marks, David I.

AU - Martino Bufarull, Rodrigo

AU - McGuirk, Joseph

AU - Mohty, Mohamed

AU - Nishihori, Taiga

AU - Nivison-Smith, Ian

AU - Rashidi, Armin

AU - Ringden, Olle

AU - Seftel, Matthew

AU - Weisdorf, Daniel

AU - Bachanova, Veronika

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AB - Older adults with B-cell acute lymphoblastic leukemia (B-ALL) have poor survival. We examined the effectiveness of reduced intensity conditioning (RIC) hematopoietic cell transplant (HCT) in adults with B-ALL age 55 years and older and explored prognostic factors associated with long-term outcomes. Using CIBMTR registry data, we evaluated 273 patients (median age 61, range 55–72) with B-ALL with disease status in CR1 (71%), >CR2 (17%) and Primary Induction Failure (PIF)/Relapse (11%), who underwent RIC HCT between 2001 and 2012 using mostly unrelated donor (59%) or HLA-matched sibling (32%). Among patients with available cytogenetic data, the Philadelphia chromosome (Ph+) was present in 50%. The 3-year cumulative incidences of nonrelapse mortality (NRM) and relapse were 25% (95% confidence intervals (CI): 20–31%) and 47% (95% CI: 41–53%), respectively. Three-year overall survival (OS) was 38% (95% CI: 33–44%). Relapse remained the leading cause of death accounting for 49% of all deaths. In univariate analysis, 3 year risk of NRM was significantly higher with reduced Karnofsky performance status (KPS <90: 34% (95% CI: 25–43%) versus KPS ≥90 (18%; 95% CI: 12–24%, P = 0.006). Mortality was increased in older adults (66+ vs. 55–60: Relative Risk [RR] 1.51 95% CI: 1.00–2.29, P = 0.05) and those with advanced disease (RR 2.13; 95% CI: 1.36–3.34, P = 0.001). Survival of patients in CR1 yields 45% (95% CI: 38–52%) at 3 years and no relapse occurred after 2 years. We report promising OS and acceptable NRM using RIC HCT in older patients with B-ALL. Disease status in CR1 and good performance status are associated with improved outcomes. Am. J. Hematol. 92:42–49, 2017.

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