A multicenter trial of myeloablative clofarabine and busulfan conditioning for relapsed or primary induction failure AML not in remission at the time of allogeneic hematopoietic stem cell transplantation

J. Magenau, P. Westervelt, S. Khaled, J. McGuirk, P. Hari, M. Eapen, P. S. Becker, B. Parkin, T. Braun, B. Logan, H. Wang, M. Jagasia, S. D. Rowley, D. D.H. Kim, T. Schechter, N. Frey, B. Scott, T. Churay, S. Lieland, S. Forman & 1 others Shin Mineishi

Research output: Contribution to journalArticle

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Abstract

Allogeneic hematopoietic cell transplantation (HCT) may produce long-term survival in AML after relapse or primary induction failure (PIF). However, outcomes of HCT performed for AML not in remission are historically poor given high relapse rates and transplant-related mortality. Preliminary studies suggest conditioning with clofarabine and myeloablative busulfan (CloBu4) may exert significant anti-leukemic effects without excessive toxicity in refractory hematologic malignancies. A prospective multicenter phase II trial was conducted to determine the efficacy of CloBu4 for patients proceeding directly to HCT with AML not in remission. Seventy-one patients (median age: 56 years) received CloBu4. At day 30 after HCT, 90% achieved morphologic remission. The incidence of non-relapse mortality and relapse at 2 years was 25% and 55%, respectively. The 2-year overall survival (OS) and event-free survival (EFS) were 26% and 20%, respectively. Patients entering HCT in PIF had significantly greater EFS than those in relapse (34% vs 8%; P<0.01). Multivariate analysis comparing CloBu4 with a contemporaneous cohort (Center for International Blood and Marrow Transplantation Research) of AML not in remission receiving other myeloablative conditioning (n=105) demonstrated similar OS (HR: 1.33, 95% confidence interval: 0.92-1.92; P=0.12). HCT with myeloablative CloBu4 is associated with high early response rates and may produce durable remissions in select patients with AML not in remission.

Original languageEnglish (US)
Pages (from-to)59-65
Number of pages7
JournalBone Marrow Transplantation
Volume52
Issue number1
DOIs
StatePublished - Jan 1 2017

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Busulfan
Hematopoietic Stem Cell Transplantation
Cell Transplantation
Multicenter Studies
Recurrence
Disease-Free Survival
Survival
Mortality
Hematologic Neoplasms
clofarabine
Multivariate Analysis
Transplantation
Bone Marrow
Confidence Intervals
Transplants
Incidence
Research

All Science Journal Classification (ASJC) codes

  • Hematology
  • Transplantation

Cite this

Magenau, J. ; Westervelt, P. ; Khaled, S. ; McGuirk, J. ; Hari, P. ; Eapen, M. ; Becker, P. S. ; Parkin, B. ; Braun, T. ; Logan, B. ; Wang, H. ; Jagasia, M. ; Rowley, S. D. ; Kim, D. D.H. ; Schechter, T. ; Frey, N. ; Scott, B. ; Churay, T. ; Lieland, S. ; Forman, S. ; Mineishi, Shin. / A multicenter trial of myeloablative clofarabine and busulfan conditioning for relapsed or primary induction failure AML not in remission at the time of allogeneic hematopoietic stem cell transplantation. In: Bone Marrow Transplantation. 2017 ; Vol. 52, No. 1. pp. 59-65.
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title = "A multicenter trial of myeloablative clofarabine and busulfan conditioning for relapsed or primary induction failure AML not in remission at the time of allogeneic hematopoietic stem cell transplantation",
abstract = "Allogeneic hematopoietic cell transplantation (HCT) may produce long-term survival in AML after relapse or primary induction failure (PIF). However, outcomes of HCT performed for AML not in remission are historically poor given high relapse rates and transplant-related mortality. Preliminary studies suggest conditioning with clofarabine and myeloablative busulfan (CloBu4) may exert significant anti-leukemic effects without excessive toxicity in refractory hematologic malignancies. A prospective multicenter phase II trial was conducted to determine the efficacy of CloBu4 for patients proceeding directly to HCT with AML not in remission. Seventy-one patients (median age: 56 years) received CloBu4. At day 30 after HCT, 90{\%} achieved morphologic remission. The incidence of non-relapse mortality and relapse at 2 years was 25{\%} and 55{\%}, respectively. The 2-year overall survival (OS) and event-free survival (EFS) were 26{\%} and 20{\%}, respectively. Patients entering HCT in PIF had significantly greater EFS than those in relapse (34{\%} vs 8{\%}; P<0.01). Multivariate analysis comparing CloBu4 with a contemporaneous cohort (Center for International Blood and Marrow Transplantation Research) of AML not in remission receiving other myeloablative conditioning (n=105) demonstrated similar OS (HR: 1.33, 95{\%} confidence interval: 0.92-1.92; P=0.12). HCT with myeloablative CloBu4 is associated with high early response rates and may produce durable remissions in select patients with AML not in remission.",
author = "J. Magenau and P. Westervelt and S. Khaled and J. McGuirk and P. Hari and M. Eapen and Becker, {P. S.} and B. Parkin and T. Braun and B. Logan and H. Wang and M. Jagasia and Rowley, {S. D.} and Kim, {D. D.H.} and T. Schechter and N. Frey and B. Scott and T. Churay and S. Lieland and S. Forman and Shin Mineishi",
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Magenau, J, Westervelt, P, Khaled, S, McGuirk, J, Hari, P, Eapen, M, Becker, PS, Parkin, B, Braun, T, Logan, B, Wang, H, Jagasia, M, Rowley, SD, Kim, DDH, Schechter, T, Frey, N, Scott, B, Churay, T, Lieland, S, Forman, S & Mineishi, S 2017, 'A multicenter trial of myeloablative clofarabine and busulfan conditioning for relapsed or primary induction failure AML not in remission at the time of allogeneic hematopoietic stem cell transplantation', Bone Marrow Transplantation, vol. 52, no. 1, pp. 59-65. https://doi.org/10.1038/bmt.2016.188

A multicenter trial of myeloablative clofarabine and busulfan conditioning for relapsed or primary induction failure AML not in remission at the time of allogeneic hematopoietic stem cell transplantation. / Magenau, J.; Westervelt, P.; Khaled, S.; McGuirk, J.; Hari, P.; Eapen, M.; Becker, P. S.; Parkin, B.; Braun, T.; Logan, B.; Wang, H.; Jagasia, M.; Rowley, S. D.; Kim, D. D.H.; Schechter, T.; Frey, N.; Scott, B.; Churay, T.; Lieland, S.; Forman, S.; Mineishi, Shin.

In: Bone Marrow Transplantation, Vol. 52, No. 1, 01.01.2017, p. 59-65.

Research output: Contribution to journalArticle

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T1 - A multicenter trial of myeloablative clofarabine and busulfan conditioning for relapsed or primary induction failure AML not in remission at the time of allogeneic hematopoietic stem cell transplantation

AU - Magenau, J.

AU - Westervelt, P.

AU - Khaled, S.

AU - McGuirk, J.

AU - Hari, P.

AU - Eapen, M.

AU - Becker, P. S.

AU - Parkin, B.

AU - Braun, T.

AU - Logan, B.

AU - Wang, H.

AU - Jagasia, M.

AU - Rowley, S. D.

AU - Kim, D. D.H.

AU - Schechter, T.

AU - Frey, N.

AU - Scott, B.

AU - Churay, T.

AU - Lieland, S.

AU - Forman, S.

AU - Mineishi, Shin

PY - 2017/1/1

Y1 - 2017/1/1

N2 - Allogeneic hematopoietic cell transplantation (HCT) may produce long-term survival in AML after relapse or primary induction failure (PIF). However, outcomes of HCT performed for AML not in remission are historically poor given high relapse rates and transplant-related mortality. Preliminary studies suggest conditioning with clofarabine and myeloablative busulfan (CloBu4) may exert significant anti-leukemic effects without excessive toxicity in refractory hematologic malignancies. A prospective multicenter phase II trial was conducted to determine the efficacy of CloBu4 for patients proceeding directly to HCT with AML not in remission. Seventy-one patients (median age: 56 years) received CloBu4. At day 30 after HCT, 90% achieved morphologic remission. The incidence of non-relapse mortality and relapse at 2 years was 25% and 55%, respectively. The 2-year overall survival (OS) and event-free survival (EFS) were 26% and 20%, respectively. Patients entering HCT in PIF had significantly greater EFS than those in relapse (34% vs 8%; P<0.01). Multivariate analysis comparing CloBu4 with a contemporaneous cohort (Center for International Blood and Marrow Transplantation Research) of AML not in remission receiving other myeloablative conditioning (n=105) demonstrated similar OS (HR: 1.33, 95% confidence interval: 0.92-1.92; P=0.12). HCT with myeloablative CloBu4 is associated with high early response rates and may produce durable remissions in select patients with AML not in remission.

AB - Allogeneic hematopoietic cell transplantation (HCT) may produce long-term survival in AML after relapse or primary induction failure (PIF). However, outcomes of HCT performed for AML not in remission are historically poor given high relapse rates and transplant-related mortality. Preliminary studies suggest conditioning with clofarabine and myeloablative busulfan (CloBu4) may exert significant anti-leukemic effects without excessive toxicity in refractory hematologic malignancies. A prospective multicenter phase II trial was conducted to determine the efficacy of CloBu4 for patients proceeding directly to HCT with AML not in remission. Seventy-one patients (median age: 56 years) received CloBu4. At day 30 after HCT, 90% achieved morphologic remission. The incidence of non-relapse mortality and relapse at 2 years was 25% and 55%, respectively. The 2-year overall survival (OS) and event-free survival (EFS) were 26% and 20%, respectively. Patients entering HCT in PIF had significantly greater EFS than those in relapse (34% vs 8%; P<0.01). Multivariate analysis comparing CloBu4 with a contemporaneous cohort (Center for International Blood and Marrow Transplantation Research) of AML not in remission receiving other myeloablative conditioning (n=105) demonstrated similar OS (HR: 1.33, 95% confidence interval: 0.92-1.92; P=0.12). HCT with myeloablative CloBu4 is associated with high early response rates and may produce durable remissions in select patients with AML not in remission.

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