Prospective trial of high-dose chemotherapy followed by infusions of peripheral blood stem cells and dose-escalated donor lymphocytes for relapsed leukemia after allogeneic stem cell transplantation.
To determine whether induction of graft-versus-host disease (GVHD) improves the outcome of acute relapsed leukemia after stem cell transplantation (SCT), we used high-dose cytarabine (ara-C) followed by infusions of donor-derived buffy coats containing peripheral blood stem cells to treat 12 patients with relapsed leukemia. Donor lymphocyte infusion (DLI) was repeated at least twice over a 5-week interval for patients in whom grade II to IV acute GVHD did not develop after the first DLI. Grade II to IV acute GVHD developed in 4 (33%) of the patients. Chronic GVHD developed in 3 patients, 2 of whom had not experienced acute GVHD. Four (67%) of the 6 patients who developed grade II to IV acute and/or chronic GVHD after DLI responded, but none of the other 6 patients responded. Four (33%) of the patients (2 with acute myelogenous leukemia [AML] and 2 with acute lymphoblastic leukemia [ALL]) achieved complete remission lasting longer than 4 months after the first DLI, but 3 of them had relapses in bone sites. Of these 4 patients, 1 patient with AML and 2 with ALL were alive 8 to 27 months after DLI. These findings indicate that high-dose ara-C combined with megadose DLI may produce durable remission of acute leukemia that has relapsed after SCT when GVHD is induced. The low induction rate of GVHD and extramedullary relapse after remission is achieved with DLI are problems yet to be solved.
Department of Cellular Transplantation Biology, Kanazawa University Graduate School of Medicine, Kanazawa, Ishikawa, Japan.
Akiyoshi
A
Takami
Hirokazu
H
Okumura
Hirohito
H
Yamazaki
Masahiro
M
Kami
Song-Wong
SW
Kim
Hidesaku
H
Asakura
Tomoyuki
T
Endo
Mitsuyuki
M
Nishio
Koichiro
K
Minauchi
Koki
K
Kumano
Naomi
N
Sugimori
Shinichiro
S
Mori
Yoshitada
Y
Takemoto
Shigeru
S
Shimadoi
Jun
J
Ozaki
Yoichi
Y
Takaue
Shinji
S
Nakao
D000328:Adult; D000964:Antimetabolites, Antineoplastic / Q000008:administration & dosage* / Q000009:adverse effects; D003561:Cytarabine / Q000008:administration & dosage* / Q000009:adverse effects; D018572:Disease-Free Survival; D005260:Female; D006086:Graft vs Host Disease / Q000209:etiology / Q000401:mortality / Q000628:therapy*; D006801:Humans; D007938:Leukemia / Q000150:complications / Q000401:mortality / Q000628:therapy*; D017710:Lymphocyte Transfusion / Q000009:adverse effects / Q000379:methods / Q000401:mortality; D008297:Male; D008875:Middle Aged; D036102:Peripheral Blood Stem Cell Transplantation / Q000009:adverse effects / Q000379:methods / Q000401:mortality; D011446:Prospective Studies; D012008:Recurrence; D012074:Remission Induction; D014184:Transplantation, Homologous; D016896:Treatment Outcome
D000964:Antimetabolites, Antineoplastic; D003561:Cytarabine