Studies of decitabine with allogeneic progenitor cell transplantation.
The aim was to determine the efficacy and safety of decitabine in the settings of relapse post-allogeneic progenitor cell transplantation or as part of the conditioning regimen. Three patients (two AML, one ALL) received single agent decitabine 1000 mg/m2 total dose) for treatment of relapse post-transplant (group 1). Median age was 32 years. Median time to relapse was 7 months. In another study four patients (three CML in an accelerated phase, one AMML) received decitabine 400 mg/m2, with busulfan 12 mg/kg and cyclophosphamide 100 mg/kg as conditioning for allogeneic stem cell transplantation (group 2). Median age was 42 years; median time to transplant was 5 months. All patients received at least 4 x 10(6) CD34+ cells from their HLA compatible donors. All patients in group 1 achieved complete remissions after decitabine therapy. The median time to neutrophil and platelet recovery were 24 and 23 days, respectively. Two patients required reinfusion of donor cells because of delayed engraftment. One patient remains alive and in remission 160 days post-decitabine therapy. Two patients in group 2 engrafted on days 23 and 25. Two patients required reinfusion of stem cells because of lack of neutrophil recovery by day 21. Two patients achieved complete cytogenetic and hematologic remission. Three patients are alive at 167,129, and 109 days post-transplant. One patient died of progressive Pseudomonas cellulitis 54 days post-initial infusion. Decitabine therapy is well tolerated in the setting of allogeneic stem cell transplantation, initial results in patients relapsing after transplant are encouraging and warrant further studies. The causes of delayed engraftment after single agent or combination therapy need to be better explored. The existence of active metabolites of decitabine which may still be present in the blood at the time of stem cell infusions, and/or insufficient immunosuppression of the preparative regimen are being explored as possible explanations for this phenomenon.
Giralt
S
S
Department of Hematology, University of Texas, MD Anderson Cancer Center, Houston 77030, USA.
Davis
M
M
O'Brien
S
S
van Besien
K
K
Champlin
R
R
de Vos
D
D
Kantarjian
H
H
D000328:Adult; D000964:Antimetabolites, Antineoplastic / Q000008:administration & dosage / Q000627:therapeutic use*; D001374:Azacitidine / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000627:therapeutic use; D003131:Combined Modality Therapy; D000077209:Decitabine; D004334:Drug Administration Schedule; D018380:Hematopoietic Stem Cell Transplantation; D006801:Humans; D007262:Infusions, Intravenous; D007938:Leukemia / Q000628:therapy*; D015464:Leukemia, Myelogenous, Chronic, BCR-ABL Positive / Q000628:therapy; D015470:Leukemia, Myeloid, Acute / Q000628:therapy; D008875:Middle Aged; D018579:Patient Selection; D054198:Precursor Cell Lymphoblastic Leukemia-Lymphoma / Q000628:therapy; D011552:Pseudomonas Infections / Q000401:mortality; D012008:Recurrence; D013997:Time Factors; D014184:Transplantation, Homologous
D000964:Antimetabolites, Antineoplastic; D000077209:Decitabine; D001374:Azacitidine