I. Applicable targets
First diagnosis of acute promyelocytic leukemia in children (ICD-10: C92.4, M9866/3).
Second, the basis of diagnosis
According to the World Health Organization Classification of Tumors. Pathology and Genetic of Tumors of Haematopoietic and Lymphoid Tissue.(2008), Diagnostic and Efficacy Criteria for Hematologic Diseases (Zhang Zhinan, Shen Ti, eds., 3rd ed., Science Press)
(I) Physical examination with or without the following signs: fever, pale skin and mucous membranes, bleeding spots and petechiae on the skin, enlarged lymph nodes and liver and spleen, sternal pressure pain, etc.
(B) Blood cell count and classification.
(C) Bone marrow examination: morphology (including histochemistry).
(iv)Immunophenotyping.
(v) Cytogenetics: karyotype analysis (t(15;17) and its variants), FISH (if necessary).
(vi) Leukemia-related genes (PML/RARa and its variants).
III. Basis for choosing treatment plan
According to the Expert Consensus on the Treatment of Acute Promyelocytic Leukemia (APL) (Chinese Medical Association, Hematology Section, Leukemia Group)
(i) Induction therapy.
1. All-trans retinoic acid (ATRA) alone or in combination with erythromycin (DNR).
ATRA: 20-30mg・m-2 ・d-1 × 28-40d;
If combined with DNR, DNR is started on day 4 after ATRA treatment, with a maximum amount of up to 135mg・m-2, split into at least 3 days of administration.
2. ATRA combined with arsenic trioxide (ATO).
ATRA:20-30mg・m-2 ・d-1×28-40d;
ATO:0.2mg・Kg-1 ・d-1×28-35d.
Cytotoxic drugs such as DNR and hydroxyurea can be added in appropriate amounts according to the changes in leukocyte count during the treatment.
(ii) Consolidation therapy after remission, 3 courses of chemotherapy are feasible, and the following regimens are available: DA regimen, MA regimen, HA regimen, DNR alone, MTZ alone, ATO combined with ATRA.
1.DA regimen:DNR 40-45mg・m-2・d-1×3d, Ara-C 100-200mg・m-2・d-1×7d;
2.MA regimen: Mitoxantrone (MTZ) 6-10mg・m-2 ・d-1×3d, Ara-C 100-200mg・m-2 ・d-1×7d;
3.HA regimen: HHT 2.0-4.0mg・m-2 ・d-1×7-9d,Ara-C 100-200mg・m-2・d-1×5-7d;
4.DNR alone: DNR 40-45mg・m-2・d-1×3d;
5.MTZ alone: MTZ 6-10mg・m-2 ・d-1×3d;
6.ATRA combined with ATO: ATRA 20-30mg・m-2 ・d-1×28d, ATO 0.2mg・Kg-1・d-1×28d.
In case of high-risk patients (WBC ≥10×109/L at initial diagnosis), Ara-C in DA or MA regimen can be replaced with 1-2g・m-2, q12h ×3d.
(C) Prevention and treatment of central nervous leukemia (CNSL): lumbar puncture and intrathecal injection at least 4 times to confirm the diagnosis of CNSL withdraw from this pathway. The sheath injection regimen is as follows.
Methotrexate (MTX): age <12 months 6mg, age 12-36 months 9mg, age >36 months 12.5mg;
Ara-C: age <12 months 15mg, age 12-36 months 25mg, age >36 months 35mg;
Dexamethasone (DXM): age <12 months 2.5mg, age 12-36 months 2.5mg, age >36 months 5mg.
(iv) Maintenance therapy after remission, sequential application of ATO, ATRA, 6-mercaptopurine (6-MP) + methotrexate (MTX) or 6-TG + Ara-C regimen for 5 cycles.
1.ATO 0.2mg・Kg-1・d-1×14-28d.
2.ATRA 20-30mg・m-2 ・d-1×14-28d.
3.6-MP+MTX or 6-TG+Ara-C.
(1)6-MP+MTX : 6-MP 50-100mg・m-2 ・d-1 for 12 weeks orally, MTX 20mg・m-2 once a week for 12 weeks;
(2) 6-TG+Ara-C: 6-TG 75 mg・m-2 ・d-1×7d, Ara-C 100 mg・m-2 ・d-1×7d.
IV. Pathway selection according to the patient’s disease status
Clinical pathway for APL in primary care children and clinical pathway for APL in children in complete remission (CR) (attached).