I. Applicable targets
Patients in the standard-risk and intermediate-risk groups with the first diagnosis of childhood acute lymphoblastic leukemia (ICD-10:C91.0).
Second, the basis of diagnosis
According to the Clinical Diagnosis and Treatment Guide-Pediatrics Internal Medicine Booklet (edited by Chinese Medical Association, People’s Health Publishing House), Zhu Futang Practical Pediatrics (7th edition) (People’s Health Publishing House), Diagnostic and Efficacy Criteria for Blood Disorders (3rd edition) (edited by Zhang Zhinan and Shen Ti, Science Publishing House).
(I) Physical examination: there may be fever, pale skin and mucous membranes, bleeding spots and petechiae on the skin, enlarged lymph nodes and liver and spleen, and sternal pressure pain.
(B) Blood cell count and classification.
(C) Bone marrow examination: morphology (including histochemical examination).
(iv)Immunophenotyping.
(V) Cytogenetics: karyotype analysis, FISH (if necessary).
(vi) Leukemia-related genes.
III. Risk grouping criteria
(i) Standard risk group: all of the following conditions must be met simultaneously.
1, age ≥ 1 year and < 10 years;
2, WBC<50×109/L;
3, good response to prednisone (peripheral blood leukemia cells <1×109/L on day 8);
4.Non-T-ALL;
5.Non-maturing B-ALL;
6, no t(9;22) or BCR/ABL fusion gene; no t(4;11) or MLL/AF4 fusion gene; no t(1;19) or E2A/PBX1 fusion gene;
7. Bone marrow showed M1 (promyelocytes <5%) or M2 (promyelocytes 5%-25%) on day 15 of treatment, and complete remission of bone marrow on day 33.
(ii) Intermediate risk group: the following 4 conditions must be met simultaneously.
1, no t(9;22) or BCR/ABL fusion gene;
2, good response to prednisone (<1×109/L peripheral blood leukemia cells on day 8);
3, bone marrow was M3 (promyelocytes >25%) on day 15 of standard risk induction remission therapy or M1/M2 on day 15 of intermediate risk induction remission therapy;
4. MRD <10-2 on day 33 if microscopic residual disease (MRD) testing is available.
Also meet at least one of the following conditions.
5, WBC ≥ 50×109/L;
6, age ≥ 10 years ;
7, T-ALL;
8, positive for t(1;19) or E2A/PBX1 fusion gene;
9, age <1 year and no MLL gene rearrangement.
(C) High-risk group: one of the following conditions must be met.
1, poor response to prednisone (peripheral blood leukemic cells >1×109/L on day 8);
2. t(9;22) or BCR/ABL fusion gene positivity;
3, t(4;11) or positive MLL/AF4 fusion gene;
4, M3 bone marrow on day 15 of intermediate-risk induction remission treatment;
5, day 33 bone marrow morphology not in remission (>5%), showing M2/M3;
6, MRD ≥ 10-2 at day 33 or MRD ≥ 10-3 at week 12 if MRD testing is available.
Fourth, the basis for selecting the treatment plan
According to the Clinical Diagnosis and Treatment Guide-Pediatrics Internal Medicine Sub-volume (edited by Chinese Medical Association, People’s Health Publishing House), Zhu Futang Practical Pediatrics (7th edition) (People’s Health Publishing House)
(I) Initial induction chemotherapy regimen.
VDLP(D) regimen.
Vincristine (VCR) 1.5mg・m-2・d-1, 1 time per week, 4 times in total, maximum absolute amount not more than 2mg each time; erythromycin (DNR) 30mg・m-2・d-1, 1 time per week, 2-4 times in total; L-asp 5000-10000u・m-2・d-1, 6-10 times in total;
Prednisone (PDN) 45-60mg・m-2・d-1, d1-28, decreasing to stop on day 29-35. Or PDN 45-60mg・m-2・d-1, d1-7, dexamethasone (DXM) 6-8mg・m-2・d-1, d8-28, decreasing to stop on day 29-35.
PDN trial d1-7, starting from 25% of the full dose, gradually increase to the full dose according to clinical response, cumulative dose >210mg・m-2 in 7 days, for patients with large tumor load can reduce the starting dose (0.2-0.5mg・kg-1・d-1) to avoid tumor lysis syndrome, d8 assessment.
(ii) Post-remission consolidation therapy.
1. CAM regimen :
Cyclophosphamide (CTX) 800-1000mg・m-2・d-1 for 1 time; Ara-C (Ara-C) 75-100mg・m-2・d-1 for 7-8 days; 6-Mercaptopurine (6-MP) 60-75mg・m-2・d-1 for 7-14 days. The CAM regimen was repeated once for patients in the intermediate risk group.
2. mM regimen.
High-dose methotrexate (MTX) 3-5g/m-2/d-1, once every two weeks for 4-5 times; calcium tetrahydrofolate (CF) 15mg/m-2 , once every 6 hours for 3-8 times, adjusted according to MTX blood levels; 6-MP 25mg/m-2/d-1 , for no more than 56 days, with dose adjustment according to WBC. Hydration and alkalinization are required during the implementation of the above protocol.
(C) Delayed intensive therapy.
1. VDLP(D) regimen: VCR 1.5mg・m-2・d-1, once a week, 3 times in total, the maximum absolute amount of each time does not exceed 2mg; DNR or Adriamycin (ADR) 25-30mg・m-2・d-1, once a week, 1-3 times in total; L-asp 5000-10000u・m-2・d-1, 4-8 times in total; PDN 45- 60mg・m-2・d-1 or DXM 6-8mg・m-2・d-1, d1-7, d15-21.
2.CAM program:
CTX 800-1000mg・m-2・d-1, 1 time; Ara-C 75-100mg・m-2・d-1 for 7-8 days; 6-MP 60-75mg・m-2・d-1 for 7-14 days. Patients in the intermediate-risk group were inserted into 8-week maintenance therapy (i.e., with an 8-week 6-MP + MTX regimen, as described below). Patients in the intermediate-risk group repeat the above VDLP(D) and CAM regimen once.
(iv) Maintenance treatment regimen.
1. 6-MP+MTX regimen: 6-MP 50mg・m-2・d-1, continuous bedtime oral on an empty stomach; MTX 15-30mg・m-2, once a week, oral or intramuscular, continued until termination of treatment (2.5-3 years for men, 2-2.5 years for women). Adjust the drug dose in the regimen according to WBC.
2. VD regimen (inserted every 4-8 weeks during 6-MP+MTX regimen).
VCR 1.5mg・m-2・d-1, 1 time, maximum absolute amount not exceeding 2mg each time; DXM 6-8mg・m-2・d-1, d1-7.
(E) Prevention and treatment of central nervous leukemia (CNSL): lumbar puncture and intrathecal injection at least 16-24 times. MTX alone or triple intrathecal injection can be used according to risk grouping with the following drug doses.
MTX: age <12 months 6 mg, age 12-36 months 9 mg, age >36 months 12.5 mg; Ara-C: age <12 months 15 mg, age 12-36 months 25 mg, age >36 months 35 mg; DXM: age <12 months 2.5 mg, age 12-36 months 2.5 mg, age >36 months 5 mg. children with CNSL diagnosed at the first diagnosis Children with CNSL diagnosed at the first diagnosis, age <1 year are not treated with radiotherapy, and those aged ≥1 year need to receive the corresponding dose of cranial radiotherapy.
V. Selection of pathway according to the patient’s disease status
The clinical pathway for primary childhood ALL and the clinical pathway for childhood ALL in complete remission (CR) (attached).
VI. Reference cost criteria
(a) The average full course reference cost standard for patients in the standard-risk group is controlled within 80,000 yuan.
(b) The average full reference cost standard for patients in the intermediate risk group is controlled within 150,000 RMB.