Treatment of Acute Lymphoblastic Leukemia in Children and Adolescents with An Anthracycline Based Regimen, but without High Doses of Cytarabine and Methotrexate: Preliminary Results of the LAFAMI-LLA-2002 Protocol.
Authors: Campos-Cabrera Gregorio , Campos-Cabrera Virgina , Campos-Villagomez Jose-Luis 
Published: October 2019

Abstract
Abstract 4104

Background
acute lymphoblastic leukemia (ALL) is the most common malignancy in children and adolescences, improvements in the 5 year survival rate continue to be seen since middle 80's, in the 1996 – 2004 SEER data reaching 84 % for children and young adults less than 19 years of age. In Mexico, a developing country, where the minimum salary is less than 3.5 dollars per day and more than a half of the population earn less than that and had no social security the need for an effective with high rate survival but low cost treatment is a priority. We developed a treatment based in the protocol ALL:SWOG9400; Blood 92(10)(Suppl.1): 676a (#2788) (1998) and Blood 100(11):756a (#2991) (2002) and weekly anthracycline induction intensification: protocol ALL-BMF90; Blood 84:3122-3133 (1994) and Blood 95:3310-3322 (2000); and named the LAFAMI-LLA-2002.

Methods
patients younger than 18 years old with ALL by bone marrow aspirate (BMA), flow cytometry and kariotype analysis; risk-based treatment assignment for children with acute lymphoblastic leukemia, (Ching-Hon Pui en J Clin Oncol 1996;14:18-24 and N Engl J Med 1998;339:605-615). Treatment with LAFAMI-LLA-2002 protocol consist in induction phase (IP) con prednisone 60 mg/m2/d for 28 days and taper to zero betwen day 29 and day 42; doxorubicine 30 mg/m2 days 1,8,15 y 22; vincristine 1.4 mg/m2 (maximum 2 mg) days 1,8,15,22,29 y 35; L-asparaginase 10,000u/m2 days 33 al 42; allopurinol 300 mg/m2 days 1 to 14; patients with high risk also receive ciclofosfamide 750 mg/m2 days 1,15 y 29; after complete IP a BMA is taken and if it is in complete remission then start CNS directed therapy with intratecal chemotherapy (IT CT) twice a week for 4 weeks, triple drug without folinic acid rescue: methotrexate 15/m2 mg, citarabine 40/m2 mg and dexametasone 8 mg; patients with positive CNS involvement and high risk patients also receive cranial irradiation (RT) 2400 cGy; maintenance initiating after IR and during IT CT with mercaptopurine 60 mg/m2/d y metotrexate 20 mg/m2 weekly during 3 years and bi monthly chemotherapy alternating one month IT CT and another month IV CT: dexametasone 40 mg/m2 days 1 to 4, ciclofosfamide 750 mg/m2 day 1, vincristine as mentioned above and citarabine 75 mg/m2 days 3 to 6 y 10 to 13; every 4 months an extra dose of doxorubicine is given with th IV CT. At the end of the treatment flow cytometry for minimal residual disease is taken and if negative go to follow up, then monthly CBC and every six months MRD by FC to complete 5 years. Echocardiograms were performed before IP and every six months until complete the end of the 5 years.

Results
from January 2002 to July 2009 13 patients were included, 8 male y 5 female, ages from 2 to 17 years; 12 B lineage an 1 T lineage; all with normal kariotype; 10 low risk and 3 high risk; 8 patients completed treatment and are in follow up, 4 patients are in maintenance phase, and one died from relapse during maintenance. All patients completed IP and CNS directed therapy, CR was demonstrated in all and each one. All 8 that completed treatment are in follow up and are negative in MRD, the minimum follow up is 13 months and the maximum is 35; 5 patients from this group have more than 24 months without treatment. No cardiac toxicity was seen; all had normal echocardiogram at the end and every six months after the end of treatment.

Conclusions
this is an efficient treatment for ALL in patients younger than 18 years, reaching until now 100% of CR in IR and CNS directed therapy; with 92.3 % of global and free event survival: similar results than in protocols using high dose cytarabine and methrotexate but without the toxicity of them; reducing financial costs and hospital admissions because it is an ambulatory treatment that can be given in almost all cities, even in developing countries.

Disclosures:
No relevant conflicts of interest to declare.