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Sequence of Cyclophosphamide (Cy) and Total Body Irradiation (TBI) Prior to Hematopoietic Cell Transplant (HCT) for Patients with Acute Leukemia: Impact upon Complications and Patient Outcome

Track: BMT Tandem "Scientific" Meeting
Wednesday, February 26, 2014, 4:45 PM-6:45 PM
Texas B (Gaylord Texan)
Jennifer L. Holter-Chakrabarty, MD , University of Oklahoma, Oklahoma City, OK
Mei-Jie Zhang, PhD , Biostatistics, Medical College of Wisconsin, Milwaukee, WI
Xiaochun Zhu, MS , CIBMTR, Medical College of Wisconsin, Milwaukee, WI
Görgun Akpek, MD, MHS , Banner MD Anderson Cancer Center, Gilbert, AZ
Mahmoud D. Aljurf, MD, MPH , King Faisal Specialist Hospital and Research Centre, Riyadh, Saudi Arabia
Andrew S. Artz, MD, MS , University of Chicago Hospitals, Chicago, IL
Frédéric Baron, MD, PhD , University of Liège, GIGA-I3, Liège, Belgium
Amber M. Borden, MD , University of Oklahoma, Oklahoma City, OK
Christopher N. Bredeson, MD, MSc , The Ottawa Hospital Blood & Marrow Transplant Program, Ottawa, ON, Canada
Christopher C. Dvorak, MD , University of California San Francisco Medical Center, San Francisco, CA
Robert B. Epstein, MD , University of Oklahoma, Oklahoma City, OK
Hillard M. Lazarus, MD , University Hospitals Case Medical Center, Cleveland, OH
Richard Olsson, MD, PhD, MMSc , Centre for Allogeneic Stem Cell Transplantation, Karolinska University Hospital, Stockholm, Sweden
Namali Pierson, MD , University of Oklahoma, Oklahoma City, OK
George B. Selby, MD , University of Oklahoma, Oklahoma City, OK
Kirsten M. Williams, MD , National Cancer Institute, NIH, Bethesda, MD
Kenneth R. Cooke, MD , Pediatric Bone Marrow Transplant, Sidney Kimmel Cancer Center, Johns Hopkins University, Baltimore, MD
Marcelo C. Pasquini, MD, MS , CIBMTR, CIBMTR/Medical College of Wisconsin, Milwaukee, WI
Philip L. McCarthy, MD , Medicine, Roswell Park Cancer Institute, Buffalo, NY
Audio File Recorded Presentation

Purpose:

The effect of sequencing Cy and myeloablative doses of TBI in the conditioning regimen on HCT outcomes in humans is unknown. In rodent experiments, however, it has been suggested that TBI followed by Cy (TBICy) is superior in reducing lung toxicity, but also results in an increased incidence of bone marrow damage. In contrast, Cy followed by TBI (CyTBI) has been reported to be associated with an improved anti-leukemic effect with increased risk of hepatic sinusoidal obstructive syndrome (SOS).

Study Design:

The sequence of Cy and TBI (1200-1500cGY) was evaluated in 1,769 recipients of related or unrelated donor HCT, younger than 60 years with acute leukemia (AML n=945, ALL= 824) who were reported to the Center for International Blood and Marrow Transplant Research (CIBMTR) from 2003 to 2010. 

Results:

A total of 948 patients received CyTBI and 821 received TBICy. The two cohorts were comparable for patient-, disease- and transplant-related characteristics (Table). The sequence of TBI did not significantly affect TRM (24% vs. 23% @3y, p=0.67; relative risk [RR] 1.01, p=0.91), leukemia relapse (27% vs. 29% @3y, p=0.34; RR 0.89, p=0.18), leukemia-free survival (48% vs. 49% @3y, p=0.27; RR 0.93, p=0.29), chronic graft vs. host disease (GVHD) (45% vs. 47% @1y, p=0.39; RR 0.9, p= 0.11) or overall survival (53% vs. 52% @3y, p=0.62; RR 0.96, p=0.57) for CyTBI and TBICy respectively. Corresponding cumulative incidences of SOS were 4% and 6% @100days (p=0.08).  While grades II-IV acute GVHD @ 100 days were 39% vs. 45% (p=0.01), multivariate analysis of grades II-IV acute GVHD resulted in a RR of 0.87 (95% CI 0.75-1.00, p=0.052). Grades III-IV acute GVHD @100 days were 16% vs. 15% (p=0.62).   Interaction between disease and conditioning sequence did not show any differential effect for AML or ALL.  

Conclusions:

This study demonstrates that the sequence of Cy and TBI does not impact transplant outcomes and complications in patients with acute leukemia undergoing myeloablative transplantation. Furthermore, the results suggest that Grades II-IV but not III-IV acute GVHD are possibly lower with CyTBI sequence, although further evaluation is warranted to confirm this finding.

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

Patient Characteristics

Cy TBI

TBI Cy

Median Age

35

34

Performance status> 90

69%

74%

AML

52%

55%

CR1

64%

64%

Ph+ ALL

25%

25%

BM stem cell source

34%

37%

HLA sibling

35%

34%

ATG

11%

13%

TBI dose 1200-1300 cGy

61%

63%

Tacrolimus/Methotrexate

43%

45%

 

Disclosures:
Nothing To Disclose
See more of: Oral Abstracts - Session A - Allogeneic Transplants
See more of: BMT Tandem "Scientific" Meeting
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