Download Reduced Mortality after Allogeneic Hematopoietic

Reduced Mortality after Allogeneic
Hematopoietic-Cell Transplantation
Ted A. Gooley, Ph.D., Jason W. Chien, M.D., Steven A. Pergam, M.D., M.P.H., Sangeeta Hingorani, M.D., M.P.H.,
Mohamed L. Sorror, M.D., Michael Boeckh, M.D., Paul J. Martin, M.D., Brenda M. Sandmaier, M.D.,
Kieren A. Marr, M.D., Frederick R. Appelbaum, M.D., Rainer Storb, M.D., and George B. McDonald, M.D.
N Engl J Med 2010;363:2091-101
R2 JUNG Myounghwa / Prof. YOON Whi Joong
INTRODUCTION
 GVHD : high mortality after allogeneic hematopoietic-cell
transplantation
 Improved prevention and treatment strategies , infection controls have
decreased the severity of acute GVHD.
 To proove improved outcomes, They compared the rates of death
not preceded by relapse, recurrent malignant conditions
in two large cohorts (1993 ~1997 VS 2003~2007)
 Frequency and severity of acute GVHD
and hepatic, renal, pulmonary, and infectious complications
in these two time periods.
METHOD
Patients
Receive first allogeneic transplant between 1993~ 1997 (Group A)
Vs receive first allogeneic transplant between 2003 ~2007 (Group B)
Transplantation Techniques
 The myeloablative regimens contained
high-dose cyclophosphamide with busulfan
or 12.0 to 13.2 Gy of total-body irradiation.
 Immunosuppressive drugs : calcineurin inhibitor plus MTX
or MMF to prevent GVHD.
 Prophylaxis infections : Antiviral ,antifungal , antibiotics agent
 To prevent cholestasis : ursodiol
METHOD
Outcome measure
 Outcome measures included overall mortality (not preceded by relapse,
recurrent malignant conditions, and the frequency and severity of
major complications.
 Mortality : Death (not preceded by relapse ) was defined as death after
transplantation
Clinical assessment & definition
Liver, Kidney, and Lung Complications through Day 100
 Liver ,kidney : Assessed according to the total bilirubin , creatinine
 Lung : Chest x-ray , Chest CT , if indicated , bronchoscopy
METHOD
Clinical assessment & definition
Viral, Bacterial, and Fungal Infections through Day 100
 CMV : viral pp65 antigen or DNA in plasma.
 one or more positive blood cultures -> considered to have gram-
negative bacteremia.
 Fungal infections : classified by international consensus criteria
 if infection : regarded as treatment failure
Acute GVHD
 GVHD grading : extent of rash, total bilirubin level, UGI symptoms,
daily stool volume.
graded as 2, 3, or 4 (mild, moderate, or severe )
METHOD
Statistical analysis
 Overall survival : Kaplan−Meier method.
 Probabilities of death : cumulative incidence curves
 Pretransplant Assessment of Mortality (PAM) score to adjust for the sev
erity of illness at the time of transplantation
 The Hematopoietic Cell Transplantation Comorbidity Index (HCT-CI) was
used for additional adjustment
RESULT
Group A Group B
Group A Group B
CONCLUSION
 Clear improvement in outcomes of transplantation
between the period from 1993 through 1997
and the period from 2003 through 2007
 Specifically, GVHD and graft-versus tumor effects,
immunologic tolerance, and the management of infection
and recurrent malignant conditions.