Priming Regiments Based on Idarubicin, or Aclacinomycin or Pirarubicin Combining with Cytarabine and Granulocyte-Colony Stimulating Factor for Reinduction of Refractory/Relapsed Acute Lymphoblastic Leukemia
Authors: Zhu Yu , He Guangsheng , Miao Kourong , Zhu Huayuan , Shen Weyi , Shuai Wang 
Published: October 2019

The refractory/relapsed acute Lymphoblastic Leukemia (ALL) is featured by high therapy difficulty and poor prognosis. The CAG regiment used for 6 refractory/relapsed T-cell ALL patients achieved very high complete remission (CR) rate[1]. So how about CAG regiment for B-cell ALL? What is the situation after the expansion of the case number? Whether the reponse rate, adverse reactions would be improved, if use other anthracyclines, such as idarubicin, pirarubicin, instead of aclacinomycin for the refractory/relapsed ALL?

So combining cytarabine and granulocyte-colony stimulating factor (G-CSF), based on idarubicin, aclacinomycin or pirarubicin respectively, the IAG, CAG or PAG were used for refractory/relapsed acute lymphoblasticleukemia, and the response rate and adverse reactions were elevated.

It was to use the priming re-induction regiment for 43 cases of refractory/relapsed acute lymphoblastic leukemia (ALL) patients (Table 1). The clinical effects and adverse reactions were evaluated by non-random use of the IAG regiment (13 cases), CAG regiment (18 cases) and TAG regiment (12 cases).

20 cases of the priming regiments are the total complete remission (CR) ones (46.5%), 7 cases are the partial remission (PR) ones (9.6%), and 16 cases are the non-remission (NR) ones (37.2%), i.e., the overall response rate (ORR) is 62.8%. Among the patients in the IAG group, 7 cases are the complete remission (CR) ones (53.8%), 2 cases are the partial remission (PR) ones (15.4%), and the overall response rate (ORR) is 69.2%. In the CAG group, there are 8 CR cases (44.4%), 3 PR cases (16.6%) with an ORR of 61%. And in the TAG group, there are 5 CR cases (41.7%), 2 PR cases (16.6%) with an ORR of 58.3%. No statistical difference is found by the comparison of ORRs among the three groups (P=0.837). There were no marked statistical difference found between the elderly group or not (60.0% vs 54.3%; P=0.272), hyperleukocytic group or not (50% vs 64.9%; P=0.808), the T cell ALL and B cell ALL (68.4% vs 54.1%; P=0.542). Current adverse reactions (Table 2), including bone marrow suppression, infection, gastrointestinal reaction and liver function impairment are tolerable after anti-infection, blood cell increase and transfusion therapy. No statistical difference is found when compared in pairs or simultaneously for the three groups.

Preliminary results show that the priming chemotherapy regimens based on small doses of anthracyclines are characterized by high remission rate, good tolerance, minor non-hematological toxic and side-effects, and definitive curative effect in the treatment of refractory/relapsed ALL patients. No statistical difference exists for the curative effects, adverse reactions, and prognosis of different anthracyclines.

Table 1. Clinical Data of Patients Clinical index CAG (n=18) IAG (n=13) TAG (n=12) P Median age (year, range) 26 (18-58) 24 (14-78) 56 (20-85) 0.008* Median number of leukocyte before the treatment (range) 3.7 (0.61-44) 6.1 (0.34-65.7) 2.18 (0.66-10.5) 0.243* Gender (case) 0.525** Male (n=31) 12 11 8 Female (n=12) 6 2 4 Immunophenotype 0.591** T cell (n=20) 7 6 7 B cell (n=23) 11 7 5 Note: *the kruskal-wallis test is adopted.

Table 2. Adverse Reactions for the Three Regiments Adverse Reaction CAG (n=18) IAG (n=13) TAG (n=12) P Hematological toxicity 1.000 Neutropenia of Level IIII-IV 18 13 12 Anemia of Level IIII-IV 18 13 12 Thrombocytopenia of Level IIII-IV 18 13 12 Gastrointestinal reaction 0.486 Level I-II 3 2 0 Level III-IV 0 0 0 Liver function impairment 0.222 Level I-II 5 1 2 Level III-IV 1 0 0 Renal function impairment Level I-II 0 0 0 Level III-IV 0 0 0 Infection 0.861 Level I-II 9 6 5 Level III-IV 0 1 0

Disclosures

No relevant conflicts of interest to declare.