Dana Farber Protocol (DFCP) for Treatment of Adolescents and Young Adults with ALL, Single Institution Experience in Saudi Arabia

Background:

Recent reports indicate that adolescents and young adults (AYA) have a better outcome when treated with pediatric protocols rather than adult ones. Many explanations were raised to explain that including the more intense pediatric protocols and different disease biology.

Patients & Methods: This is a retrospective study that included AYA patients diagnosed as ALL and treated at King Abdulla Medical City (KAMC),Saudi Arabia, in the period from mid 2011- March 2015.

Results: 37 patients were included in this study including 25 males and 12 females with a ratio of 2:1. The median age at diagnosis was 19.4 y. At presentation the mean number of WbCs was 63.7 x 10⁹/L + 103.4 (range 1.9 to 500,000 x10⁹/L), HB 8.87 + 2.3 gm/L (range 6.5-15.2 gm/L), platelets 59 x 10⁹/L + 43.9 (range 8-100,000 x10⁹/L. Bone marrow blasts ranged from 35 -99% with a mean and median of 80.3 + 18.5, 84 % respectively. B-cell phenotype constituted the majority of cases 29/37(78.3%). Cytogenetics using karyotyping and FISH Panel for ALL (done in Mayo clinic,USA) revealed Very high risk cytogenetics (Philadelphia, MLL, complex cytogenetics, hypodiploidy in 14/37 (37.8%) patients, Intermediate / high 16 patients (43.2%) and 7 (18.9%) with favorable cytogenetics (hyperdiploidy, tetraploidy, del p16).

Complete remission was confirmed in 35 of 37 patients (94.5%). (one did not achieve remission while response was not evaluable in another patient who died during induction due to hepatic failure). Repeat cytogenetics at the time of D28 BM evaluation was done in 29/37 patients while in 8/37 it was not done for technical reasons. Cytogenetic remission was confirmed in 18 out of 21 with cytogenetic abnormality (85.7%).

After a median follow up period of 12 m (range 3-52.5 m).. Leukemia free survival ranged from 3 to 52.5 m with a median of 10.5 m, mean 17.5 {CI (95%) 12.61-22.53}: while median survival was 12m with a mean of 18.5m {CI (95%) 13.6-23.5}.

As a whole 6 cases relapsed (5 in the first 18 m and 1 after 4 Y) and 1 was primary resistant constituting (7/35 18.9% of cases) while response could not be documented in one patient who died during induction. Of the 6 relapsed cases, 4 of them due to disease progression and non-responsive to salvage treatment or transplant procedure

Toxicity included febrile neutropenia in virtually all patients with negative cultures in 20/37 patients (54%) while Gram negative sepsis was confirmed in 12/37 patients (32%). Major complications occurred in 9/37 patients (24.3%) and include: septic shock that required ICU (1 patient), typhilitis (1 patient), pancreatitis (2 patients), avascular necrosis of head of femur (2 patients).neuropathy ≥ GIII (2 patients)

In conclusion: Although DFCP is an effective treatment for AYA with ALL, Yet toxicity can not be overlooked.