Increased risk of chronic graft-versus-host disease, obstructive bronchiolitis, and alopecia with busulfan versus total body irradiation: long-term results of a randomized trial in allogeneic marrow recipients with leukemia. Nordic Bone Marrow Transplantation Group.
Leukemic patients receiving marrow from HLA-identical sibling donors were randomized to treatment with either busulfan 16 mg/kg (n = 88) or total body irradiation ([TBI] n = 79) in addition to cyclophosphamide 120 mg/kg. The patients were observed for a period of 5 to 9 years. Busulfan-treated patients had an increased risk of veno-occlusive disease (VOD) of the liver (12% v 1%, P =.01) and hemorrhagic cystitis (32% v 10%, P =.003). Acute graft-versus-host disease (GVHD) was similar in the two groups, but the 7-year cumulative incidence of chronic GVHD was 59% in the busulfan-treated group versus 47% in the TBI group (P =.05). Death from GVHD was more common in the busulfan group (22% v 3%, P <.001). Obstructive bronchiolitis occurred in 26% of the busulfan patients but in only 5% of the TBI patients (P <.01). Complete alopecia developed in 8 busulfan patients and partial alopecia in 17, versus five with partial alopecia in the TBI group (P <.001). Cataracts occurred in 5 busulfan-treated patients and 16 TBI patients (P =.02). The incidence of relapse after 7 years was 29% in both groups. Seven-year transplant-related mortality (TRM) in patients with early disease was 21% in the busulfan group and 12% in the TBI group. In patients with more advanced disease, the corresponding figures were 64% and 22%, respectively (P =.004). Leukemia-free survival (LFS) in patients with early disease was 68% in busulfan-treated patients and 66% in TBI patients. However, 7-year LFS in patients with more advanced disease was 17% in the busulfan group versus 49% in the TBI group (P <.01). In patients with chronic myeloid leukemia (CML) in first chronic phase, 7-year LFS was 72% and 83% in the two groups, respectively.
Ringdén
O
O
Centre for Allogeneic Stem Cell Transplantation, and the Department of Hematology, Karolinska Institute, Huddinge Hospital, Huddinge, Sweden. olle.ringden@immunlab.hs.sll.se
Remberger
M
M
Ruutu
T
T
Nikoskelainen
J
J
Volin
L
L
Vindeløv
L
L
Parkkali
T
T
Lenhoff
S
S
Sallerfors
B
B
Mellander
L
L
Ljungman
P
P
Jacobsen
N
N
D000293:Adolescent; D000328:Adult; D000505:Alopecia / Q000453:epidemiology / Q000209:etiology*; D016026:Bone Marrow Transplantation / Q000009:adverse effects; D001989:Bronchiolitis Obliterans / Q000453:epidemiology / Q000209:etiology*; D002066:Busulfan / Q000008:administration & dosage / Q000009:adverse effects*; D002386:Cataract / Q000453:epidemiology / Q000209:etiology; D002423:Cause of Death; D002648:Child; D002675:Child, Preschool; D002908:Chronic Disease; D003556:Cystitis / Q000453:epidemiology / Q000209:etiology; D018572:Disease-Free Survival; D005260:Female; D005500:Follow-Up Studies; D006086:Graft vs Host Disease / Q000453:epidemiology / Q000209:etiology*; D006504:Hepatic Veno-Occlusive Disease / Q000453:epidemiology / Q000209:etiology; D006648:Histocompatibility; D006801:Humans; D015994:Incidence; D007223:Infant; D007938:Leukemia / Q000628:therapy*; D017563:Lung Diseases, Interstitial / Q000209:etiology / Q000401:mortality; D008297:Male; D008875:Middle Aged; D009102:Multiple Organ Failure / Q000209:etiology / Q000401:mortality; D011832:Radiation Injuries / Q000453:epidemiology / Q000209:etiology*; D012008:Recurrence; D012306:Risk; D016019:Survival Analysis; D019172:Transplantation Conditioning / Q000009:adverse effects* / Q000379:methods; D014184:Transplantation, Homologous; D016896:Treatment Outcome; D014916:Whole-Body Irradiation
D002066:Busulfan