[Abstract
OBJECTIVE: To investigate the efficacy and toxic effects of pirarubicin combined with cytarabine (TA) regimen and TOLP regimen in the treatment of primary acute leukemia (acute gonorrhea and acute non-gonorrhea leukemia).
METHODS: Seventy-two cases of primary acute leukemia were treated with the TA and TOLP regimens. Among them, 23 cases of ALL were treated with TOLP regimen and 49 cases of AML were treated with TA regimen.
RESULTS: Among the 72 leukemia cases, 49 cases achieved complete remission (CR), with a CR rate of 68.1%; 11 cases achieved PR (PR rate of 15.3%). The total effective rate (CR+PR) was 83.3%. 18 of 23 ALL cases achieved CR (CR rate 78.3%), 3 cases achieved PR (PR rate 13.1%), the total effective rate (CR+PR) was 91.4%. 31 of 49 AML cases achieved CR (CR rate 63.3%), 8 cases achieved PR (PR rate 16.3%), the total effective rate (CR+PR) was 79.5%. The total effective rate (CR+PR) was 79.5%. Toxic side effects were mainly bone marrow suppression, gastrointestinal symptoms and mild liver function abnormalities.
Conclusion: The TA regimen can be used for the treatment of primary acute leukemia with good efficacy and mild toxic side effects, which can be tolerated by patients.
INTRODUCTION: The use of anthracyclines in acute leukemia has led to a significant increase in the rate of complete remission and long-term survival in acute leukemia. The classic regimens for the treatment of acute leukemia are the DA (erythromycin + cytarabine) regimen and the DOLP regimen, which have complete remission rates of 60-70% …… Pirarubicin (THP), a new class of semi-synthetic anthracycline antitumor drugs [1]. It can rapidly enter into tumor cells with high distribution concentration, so it has strong anticancer activity and wide anticancer spectrum, and the toxic side effects such as myocardial toxicity, gastrointestinal tract and hair loss are significantly lower than those of adriamycin. In this study, we applied TA regimen and TOLP regimen for the treatment of primary acute leukemia to observe its efficacy and toxic side effects.
1. Data and methods
1.1 Clinical data: 72 cases (from PLA General Hospital, PLA 304 Hospital, Beijing Friendship Hospital, Beijing Tongren Hospital, Beijing Military General Hospital), 41 males and 31 females; age 34.8 years (2-65 years); typed according to the diagnostic criteria of acute leukemia by clinical, cytomorphological and immunophenotyping tests [2]. There were 23 cases of ALL (including 10 cases of L1, 8 cases of L2, 2 cases of L3, and 3 cases of lymphoma leukemia) and 49 cases of AML (including 7 cases of M1, 13 cases of M2, 8 cases of M4, 15 cases of M5, 3 cases of M6, 1 case of mixed cell leukemia, and 2 cases of slow-onset acute transformation).
1.2 Chemotherapy regimen and dose.
Primary ANLL was treated with TA regimen: THP 25-30 mg/m2,d1 C3; Ara-C 150 mg/m2,d1-7.
Primary ALL was treated with TOLP regimen: THP25-30 mg/m2,d1C3;VCR 1.4mg/m2,1 time/week×4;L-ASP6000U/m2,d19-25;prednisone 40mg/m2,d1-28
1.3 Observation index
1.Efficacy observation: According to the standards set by the National Society of Hematology, the peripheral blood and bone marrow images were classified into three levels of complete remission (CR), partial remission (PR) and non-remission (NR) according to the patients’ clinical performance, and CR+PR was the total effective rate.
2.Observation of side effects: The patients were observed and recorded before and after chemotherapy for decreased appetite, stomach upset, nausea, vomiting, palpitation, chest tightness, abdominal pain, diarrhea, hair loss, oral mucosal ulceration, erosion and other toxic side effects.
3. Laboratory tests.
①Change of peripheral blood picture before and after chemotherapy.
②Change of bone marrow before and after chemotherapy.
③ Changes in liver and kidney function before and after chemotherapy.
④Changes in chest X-ray, electrocardiogram and abdominal ultrasound before and after chemotherapy.
2.Results
2.1 Efficacy (1) Among 72 cases of leukemia, 49 cases achieved CR, with a CR rate of 68.1%; 11 cases achieved PR (PR rate of 15.3%). The total effective rate (CR+PR) was 83.3%. (2) Among 23 cases of ALL, 18 cases achieved CR (CR rate of 78.3%) and 3 cases achieved PR (PR rate of 13.1%), with an effective rate (CR+PR) of 91.4%. (3) Among 49 cases of AML, 31 cases achieved CR (CR rate 63.3%) and 8 cases achieved PR (PR rate 16.3%), and the effective rate (CR+PR) was 79.5%.
2.2 Side effects The main side effect of TA/TOLP regimen for acute leukemia was myelosuppression, with an incidence of 94.4% (68/72 cases). The incidence of gastrointestinal side effects such as nausea, vomiting and diarrhea was 51.4% (37/72 cases); the incidence of oral ulcers was 12.5% (9/72 cases); the incidence of mild abnormal liver function (GTP>50-200, GOP>50-200) was 11.1% (8/72 cases); the incidence of electrocardiogram abnormalities was 2.7% (2 cases); the incidence of alopecia The incidence of alopecia was 6.9% (5/72 cases). One of the null cases died of intracranial hemorrhage.
The time to WBC50×309/L was 15.3 (10-24) d in 63/72 (87.5%) patients.
3. Discussion
Pyrrolizidine is a derivative of adriamycin, whose chemical structure is obtained by attaching a tetrahydropyranyl group to the 4′-0-position of adriamycin to obtain (2’R)- 4′-0-tetrahydropyranyl adriamycin. This drug mainly inhibits DNA synthesis by directly embedding between DNA double strands and/or inhibiting DNA polymerase, thus inhibiting DNA replication and transcription [1].Yamada et al [3] found in a phase II clinical study that THP alone treated 21 patients with acute leukemia, 3 CR,4 PR, with an efficiency rate of 30%.Ohno et al [4] applied THP to treat acute leukemia. The CR rate was 18.6% and the PR rate was 35.8%. Domestic scholars [5,6] used pirarubicin combined with cytarabine to treat acute leukemia and achieved significant results.
In our group, we treated 72 primary acute leukemia patients with TA/TOLP regimen, including 23 cases of ALL (including 10 cases of L1, 8 cases of L2, 2 cases of L3, and 3 cases of lymphoma leukemia) and 49 cases of AML (including 7 cases of M1, 13 cases of M2, 8 cases of M4, 15 cases of M5, 3 cases of M6, 1 case of mixed cell leukemia, and 2 cases of slow-onset acute transformation). The results showed that 49 of 72 leukemia cases achieved CR (CR rate 68.1%) and 11 achieved PR (PR rate 15.3%), with an overall effective rate (CR+PR) of 83.3%. 18 of 23 ALL cases achieved CR (CR rate 78.3%) and 3 achieved PR (PR rate 13.1%), with an overall effective rate (CR+PR) of 91.4%. 49 leukemia cases achieved CR (CR rate 15.3%) and 11 achieved PR (PR rate 15.3%), with an overall effective rate (CR+PR) of 83.3%. The high efficacy of ALL was associated with the presence of 10 pediatric ALL cases.
The main side effect of TA/TOLP regimen for acute leukemia was myelosuppression, with an incidence of 94.4% (68/72 cases). The incidence of gastrointestinal side effects such as nausea, vomiting and diarrhea was 51.4% (37/72 cases); the incidence of oral ulcers was 12.5% (9/72 cases); the incidence of mild abnormal liver function (GTP>50-200, GOP>50-200) was 11.1% (8/72 cases); the incidence of ECG abnormalities was 2.7% (2 cases); the incidence of alopecia The incidence of alopecia was 6.9% (5/72 cases). One of the null cases died of intracranial hemorrhage.
The time to WBC50×309/L was 15.3 days (10-24 days) in 63/72 patients (87.5%).
From the results of this paper, we analyzed that pirarubicin is a new anthracycline that is more acceptable for leukemia patients. TA/TOLP regimen for acute leukemia has better efficacy and less toxic side effects, especially cardiotoxicity and alopecia [3,4], which can be tolerated by patients and can be used for the treatment of primary acute leukemia. However, the number of cases in this paper is limited, and its efficacy and toxic side effects have yet to be further explored by accumulating more cases.