[Glivec in combination with HA regimen for treatment of 20 patients with Ph chromosome positive acute leukemia].
OBJECTIVE
Glivec was approved by Food & Drug Administration (FDA) in May 2001 as a gene target drug for treatment of chronic myeloid leukemia (CML) and showed a good curative effect for patients with chronic myeloid leukemia in chronic phase. But its effectiveness was poor in patients with CML blast phase treated with Glivec alone. Glivec was reported having synergetic effect with other chemical agents in vitro, but there is few report in clinical combined application. In this paper, we analyzed effectiveness of Glivec in combination with homoharringtonine (HHT) and cytarabine (Ara-C) for patients with Ph chromosome positive acute leukemia (Ph(+)-AL), and investigated patients' tolerance to side effects of this trial.


METHODS
A total of 20 patients (16 males and 4 females, median age was 43 years) were eligible. Blasts in peripheral blood (PB) or bone marrow (BM) were both more than 30%, bcr/abl fusion genes were detected positive in 90% cells by analysis of karyotype or fluorescence in situ hybridization (FISH). Five patients showed t(9;22) and other 15 patients showed more complicated chromosome abnormality. Of these 20 patients, 17 patients developed Ph(+)-ANLL from CML, 1 case developed Ph(+)-ALL, and other 2 cases were primary Ph(+)-ALL. The median interval from diagnosis to Glivec treatment was 4 months. Eighteen of 20 patients received different chemotherapy regimens for 2-4 treatment cycles, but no one reached hematological complete remission (HCR). All patients were given oral Glivec daily at the doses of 0.3-0.6 g in a median treatment time of 2.5 months (range, 1-6.5 months). Ph(+)-ANLL patients were infused with HHT over 6-24 hours daily at the doses of 1-2 mg intravenously and Ara-C 30-50 mg daily subcutaneously for 10-14 days; 3 patients with Ph(+)-ALL received HOAP or DOP combination treatment regimens (One cycle consists of HA with the same dosage described above for Ph(+)-ANLL patients for 7 days, daunorubicin at the dose of 40 mg/d intravenously for 3 days, vincristine at the dose of 2 mg/wk for two weeks, and prednisone at the doses of 60-80 mg/d for 14 days). Median treatment cycle was 2 (range, 1-3). The dosage of Glivec could be reduced or treatment was suspended when bone marrow inhibition happened. G-CSF was used when necessary. The curative effect was evaluated by international hematology and cytogenetics standards, in which bone marrow was examined every chemotherapy cycle and chromosome was analyzed 3 months later.


RESULTS
Among the 20 patients receiving Glivec, 40% achieved HCR, and 25% achieved hematological partial remission (HPR), but only 15% patients approached a partial cytogenetic remission and no cytogenetic responses were found in other 85% patients. White blood cells (WBC) in peripheral blood reduced from 41+/-31 x 10(9)/L to normal level within 1 week. The blasts decreased from (50+/-30)% to(1.9+/-2.9)% (P< 0.001) in median time of 21.0+/-16.8 days. Three patients with high fever recovered normal temperature after 3 days treatment. When follow-up median time at 8 months, the total survival rate reduced to 40%, the rate of death and lost follow-up number of patients added to 60%.


CONCLUSIONS
Regimen of Glivec in combination with HA could increase chemotherapy effect for the patients with Ph(+)-AL, prolong their life time and the side-effects were tolerable.
Meng
Fan-Yi
FY
Department of Hematology, Nanfang Hospital, The First Military Medical University, Guangzhou, Guangdong, 510515, PR China. mengfy@fimmu.com
Zheng
Wei-Yang
WY
Liu
Xiao-Li
XL
Song
Lan-Lin
LL
Xu
Bing
B
Zhang
Yu
Y
Huang
Fen
F
D000208:Acute Disease; D000293:Adolescent; D000328:Adult; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D001549:Benzamides; D005260:Female; D005500:Follow-Up Studies; D006248:Harringtonines / Q000008:administration & dosage* / Q000009:adverse effects; D000077863:Homoharringtonine; D006801:Humans; D000068877:Imatinib Mesylate; D007938:Leukemia / Q000097:blood / Q000188:drug therapy* / Q000235:genetics; D008297:Male; D008875:Middle Aged; D010677:Philadelphia Chromosome; D010879:Piperazines / Q000008:administration & dosage* / Q000009:adverse effects; D011743:Pyrimidines / Q000008:administration & dosage* / Q000009:adverse effects
D001549:Benzamides; D006248:Harringtonines; D010879:Piperazines; D011743:Pyrimidines; D000077863:Homoharringtonine; D000068877:Imatinib Mesylate