Multicenter prospective study of interferon-alpha and conventional chemotherapy versus bone marrow transplantation for newly diagnosed patients with chronic myelogenous leukemia. Kouseisho Leukemia Study Group.
We compared interferon-alpha (IFN-alpha therapy with bone marrow transplantation (BMT) after initial conventional chemotherapy in patients with chronic myelogenous leukemia (CML) in a multicenter prospective study. Ninety patients with Philadelphia chromosome-positive CML in chronic phase were enrolled between 1991 and 1994. Sixty-six of 89 evaluable patients received IFN-alpha after conventional chemotherapy with hydroxyurea or busulfan (IFN-alpha group). Twenty-three patients received allogeneic BMT (BMT group). Fifteen of them received transplants from HLA-identical family donors and 8 from HLA-matched unrelated donors. Forty-seven of 66 patients (71%) in the IFN-alpha group and 17 of 23 patients (74%) in the BMT group achieved complete hematologic response, and 12% in the IFN-alpha group and 13% in the BMT group achieved partial hematologic response. Complete cytogenetic response was induced in 5 (8%), partial cytogenetic response in 8 (12%), and minor cytogenetic response in 12 (18%) in the IFN-alpha group. At a median follow-up of 54 months (range, 30-76 months), in the IFN-alpha group, the predicted 6-year survival rate was 54.5% and the predicted 6-year rate of those remaining in chronic phase was 45.7%. Compared with patients with no cytogenetic response, the patients with some cytogenetic response after IFN-alpha treatment had significantly superior survival and duration of the chronic phase even after correction for the time to response using landmark analysis (P < .05). In the BMT group, the predicted 5-year survival rate was 93.3% for family-donor BMT and 21.9% for unrelated-donor BMT Acute graft-versus-host disease of grade III or IV was observed in 1 of 15 patients who received family-donor BMT and 3 of 8 patients who received unrelated donor BMT. Prior treatment with conventional cytotoxic drugs induced early hematologic response and did not reduce the effect of IFN-alpha on CML. Unrelated-donor transplantation should be offered to some patients according to patient age, HLA-matching status, time from diagnosis to BMT, and risk factors.
Ohnishi
K
K
Department of Medicine III, Hamamatsu University School of Medicine, Japan. kohnishi@hama-med.ac.jp
Minami
S
S
Ueda
T
T
Nishimura
M
M
Tsubaki
K
K
Takemoto
Y
Y
Takeshita
A
A
Sao
H
H
Kageyama
S
S
Ueda
R
R
Ohno
R
R
D000293:Adolescent; D000328:Adult; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D016026:Bone Marrow Transplantation / Q000592:standards*; D020732:Cytogenetic Analysis; D005260:Female; D006801:Humans; D016898:Interferon-alpha / Q000627:therapeutic use*; D007564:Japan; D015464:Leukemia, Myelogenous, Chronic, BCR-ABL Positive / Q000453:epidemiology / Q000628:therapy*; D008297:Male; D011446:Prospective Studies; D012074:Remission Induction; D015996:Survival Rate; D014184:Transplantation, Homologous; D016896:Treatment Outcome
D000970:Antineoplastic Agents; D016898:Interferon-alpha