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Comparative Study
. 2016 Mar;91(3):322-9.
doi: 10.1002/ajh.24285.

Pediatric-inspired therapy compared to allografting for Philadelphia chromosome-negative adult ALL in first complete remission

Matthew D Seftel  1 , Donna Neuberg  2 , Mei-Jie Zhang  3   4 , Hai-Lin Wang  3 , Karen Kuhn Ballen  5 , Julie Bergeron  6 , Stephen Couban  7 , César O Freytes  8 , Mehdi Hamadani  3 , Mohamed A Kharfan-Dabaja  9 , Hillard M Lazarus  10 , Taiga Nishihori  9 , Kristjan Paulson  1 , Wael Saber  3 , Stephen E Sallan  11 , Robert Soiffer  12 , Martin S Tallman  13 , Ann E Woolfrey  14 , Daniel J DeAngelo  12 , Daniel J Weisdorf  15 ; Acute Leukemia Committee of the CIBMTR and the Dana Farber ALL Consortium
Affiliations
Comparative Study

Pediatric-inspired therapy compared to allografting for Philadelphia chromosome-negative adult ALL in first complete remission

Matthew D Seftel et al. Am J Hematol. 2016 Mar.

Abstract

For adults with Philadelphia chromosome-negative (Ph-) acute lymphoblastic leukemia (ALL) in first complete remission (CR1), allogeneic hematopoietic cell transplantation (HCT) is an established curative strategy. However, pediatric-inspired chemotherapy may also offer durable leukemia-free survival in the absence of HCT. We compared 422 HCT recipients aged 18-50 years with Ph-ALL in CR1 reported to the CIBMTR with an age-matched concurrent cohort of 108 Ph- ALL CR1 patients who received a Dana-Farber Consortium pediatric-inspired non-HCT regimen. At 4 years of follow-up, incidence of relapse after HCT was 24% (95% CI 19-28) versus 23% (95% CI 15-32) for the non-HCT (chemo) cohort (P=0.97). Treatment-related mortality (TRM) was higher in the HCT cohort [HCT 37% (95% CI 31-42) versus chemo 6% (95% CI 3-12), P<0.0001]. DFS in the HCT cohort was 40% (95% CI 35-45) versus 71% (95% CI 60-79) for chemo, P<0.0001. Similarly, OS favored chemo [HCT 45% (95% CI 40-50)] versus chemo 73% [(95% CI 63-81), P<0.0001]. In multivariable analysis, the sole factor predictive of shorter OS was the administration of HCT [hazard ratio 3.12 (1.99-4.90), P<0.0001]. For younger adults with Ph- ALL, pediatric-inspired chemotherapy had lower TRM, no increase in relapse, and superior overall survival compared to HCT. Am. J. Hematol. 91:322-329, 2016. © 2015 Wiley Periodicals, Inc.

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Conflict of interest statement

Conflict-of-interest disclosure: The authors do not have conflicts of interest to declare.

Figures

Figure 1
Figure 1
Overall Schema of the Dana Farber Cancer Institute (DFCI) adult ALL Consortium regimens in trials 01-175 and 06-254 trials, CNS: Central Nervous System; IT: Intrathecal; XRT: Cranial Irradiation; ASP: L-Asparaginase; CR: Complete Remission; PEG: Pegylated; HDMTX: High dose Methotrexate; BFML Berlin-Frankfurt-Münster; HiDAC: High dose cytarabine;
Figure 2
Figure 2
Comparison of outcomes of Chemotherapy only regimen (chemo) and allogeneic hematopoietic cell transplantation (HCT) (a) Overall Survival (b) Disease Free Survival (c) Cumulative Incidence of Relapse (d) Cumulative Incidence of Treatment Related Mortality (e) Kaplan Meier Estimate of Overall Survival Comparing Chemotherapy Patients To Sub-Groups Of HCT Recipients
Figure 2
Figure 2
Comparison of outcomes of Chemotherapy only regimen (chemo) and allogeneic hematopoietic cell transplantation (HCT) (a) Overall Survival (b) Disease Free Survival (c) Cumulative Incidence of Relapse (d) Cumulative Incidence of Treatment Related Mortality (e) Kaplan Meier Estimate of Overall Survival Comparing Chemotherapy Patients To Sub-Groups Of HCT Recipients
Figure 2
Figure 2
Comparison of outcomes of Chemotherapy only regimen (chemo) and allogeneic hematopoietic cell transplantation (HCT) (a) Overall Survival (b) Disease Free Survival (c) Cumulative Incidence of Relapse (d) Cumulative Incidence of Treatment Related Mortality (e) Kaplan Meier Estimate of Overall Survival Comparing Chemotherapy Patients To Sub-Groups Of HCT Recipients
Figure 2
Figure 2
Comparison of outcomes of Chemotherapy only regimen (chemo) and allogeneic hematopoietic cell transplantation (HCT) (a) Overall Survival (b) Disease Free Survival (c) Cumulative Incidence of Relapse (d) Cumulative Incidence of Treatment Related Mortality (e) Kaplan Meier Estimate of Overall Survival Comparing Chemotherapy Patients To Sub-Groups Of HCT Recipients
Figure 2
Figure 2
Comparison of outcomes of Chemotherapy only regimen (chemo) and allogeneic hematopoietic cell transplantation (HCT) (a) Overall Survival (b) Disease Free Survival (c) Cumulative Incidence of Relapse (d) Cumulative Incidence of Treatment Related Mortality (e) Kaplan Meier Estimate of Overall Survival Comparing Chemotherapy Patients To Sub-Groups Of HCT Recipients
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