Cyclosporine and mycophenolate mofetil prophylaxis with fludarabine and melphalan conditioning for unrelated donor transplantation: a prospective study of 22 patients with hematologic malignancies.
In an attempt to decrease toxicity in high-risk patients undergoing unrelated donor hematopoietic stem cell transplantation (URD HSCT), we tested a combination of cyclosporine (CSP) and mycophenolate mofetil (MMF) as graft-versus-host disease (GVHD) prophylaxis with the reduced-intensity conditioning regimen fludarabine/melphalan (Flu/Mel). A total of 22 adult patients with advanced myeloid (n=15) and lymphoid (n=7) malignancies were treated. All patients received Flu 25 mg/m2 for 5 days and Mel 140 mg/m2, with CSP 3 mg/kg daily and MMF 15 mg/kg three times a day. The median age was 49 years (range 18-66). Durable engraftment was seen in all but one patient with myelofibrosis. The 1-year nonrelapse mortality was 32%, 27% from GVHD. The cumulative incidence of acute GVHD grade 2-4 and 3-4 was 63 and 41%, respectively. With a median follow-up of 18 months, the disease-free survival (DFS) and overall survival (OS) are 55 and 59%, respectively. For patients with AML and MDS (n=14), the DFS and OS is 71%. For patients undergoing a second transplant (n=14), the DFS and OS is 57%. In conclusion, this regimen is associated with acceptable toxicity but high rates of GVHD in high-risk patients undergoing URD HSCT. Encouraging disease control for patients with advanced myeloid malignancies was observed.
Rodriguez
R
R
City of Hope National Medical Center, Duarte, CA 91010, USA. robertorodriguez@coh.org
Parker
P
P
Nademanee
A
A
Smith
D
D
O'Donnell
M R
MR
Stein
A
A
Snyder
D S
DS
Fung
H C
HC
Krishnan
A Y
AY
Popplewell
L
L
Cohen
S
S
Somlo
G
G
Angelopoulou
M
M
Al-Kadhimi
Z
Z
Falk
P M
PM
Spielberger
R
R
Kogut
N
N
Sahebi
F
F
Senitzer
D
D
Slovak
M
M
Schriber
J
J
Forman
S J
SJ
D000293:Adolescent; D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use / Q000633:toxicity*; D016572:Cyclosporine / Q000008:administration & dosage; D005260:Female; D006085:Graft Survival; D006086:Graft vs Host Disease / Q000517:prevention & control; D019337:Hematologic Neoplasms / Q000150:complications / Q000401:mortality / Q000628:therapy*; D018380:Hematopoietic Stem Cell Transplantation / Q000009:adverse effects / Q000379:methods* / Q000401:mortality; D006801:Humans; D008297:Male; D008558:Melphalan / Q000008:administration & dosage; D008875:Middle Aged; D009173:Mycophenolic Acid / Q000008:administration & dosage / Q000031:analogs & derivatives*; D009894:Opportunistic Infections; D011292:Premedication / Q000379:methods*; D011446:Prospective Studies; D016019:Survival Analysis; D014019:Tissue Donors; D019172:Transplantation Conditioning / Q000379:methods*; D016896:Treatment Outcome; D014740:Vidarabine / Q000008:administration & dosage / Q000031:analogs & derivatives*
D016572:Cyclosporine; D014740:Vidarabine; D009173:Mycophenolic Acid; C024352:fludarabine; D008558:Melphalan