Adolescent and young adult (AYA) ALL patients represent a special patient group, as they may receive chemotherapy based on either pediatric or adult chemotherapy protocol [13]. The favorable outcomes found in children, coupled with unfavorable outcomes noticed in AYA, generated the idea for practical use of pediatric protocols among AYA. Also, many novel drugs such as Blinatumomab, inotuzomab, and chimeric antigen receptor T cell have been established to improve outcomes in poorly responding, relapsed, or refractory B cell ALL [14].
In ALL, AYA patients have poorer EFS and OS compared to children, because AYA tends to have unfavorable characteristics, such as T cell phenotype, more incidence of Philadelphia chromosome (9;22), and less occurrence of favorable chromosomal abnormalities such as hyperdiploidy [15]. In our study, immunophenotyping study revealed 26.83% of our patients were T-ALL, and 19.51% were Philadelphia chromosome-positive. These results coincide to a great extent with literatures, as in adults, T-ALL accounts for about 25% of cases, also Philadelphia chromosome in adults ALL can range from 15 to 50% increasing with age [16].
Several retrospective studies have shown that AYA patients who received pediatric protocols have better outcomes (CR 90–99% and EFS 63–80%) when compared with AYA patients who received adult protocols (CR 80–94% and EFS 34–71%) [17]. Although, one study by Usvasalo et al. [17] showed no superiority of both pediatric and adult protocols regarding CR and EFS.
Several factors may clarify better outcomes in pediatric protocols. Firstly, pediatric protocols have more non-myelosuppressive drugs with more activity on leukemic cells particularly during the BM suppression phase induced by anti-metabolites and anthracyclines. Moreover, in pediatric protocols, CNS prophylaxis as intrathecal methotrexate was administered earlier, more frequently, and for a longer time as CNS is the shelter for blast cells. Also, the maintenance therapy period is shorter in adult protocols [18, 19].
In our study, forty-one patients received the pediatric protocol DFCP, Thirty-eight patients (92.68%) achieved complete CR, eleven patients (26.83%) relapsed, and ten (24.39%) patients died. One-, two-, and three-year EFS were 75.61%, 72.91%, and 67.51% respectively. One-, two-, and three-year OS were 85.3%, 77.26%, and 74.39% respectively.
These results coincide to a great extent with some differences reported in many studies. DeAngelo et al. [20] used DFCP for the treatment of 74 adult patients (18–50 years) with ALL. Eighty-four percent of the patients achieved CR, with 2-year EFS and OS of 72.5% and 77.1%, respectively.
Barry et al. [11] treated 51 de novo ALL patients (15–18 years) with by DFCP, and found that the 5-year EFS and OS were 77.5% and 81% respectively. Also, Storring et al. [21] used a modified DFCP in 68 patients (17–71 years), 82% of the patients achieved CR, with 3-year EFS and OS of 77% and 65%, respectively.
Furthermore, Al-Khabori et al. [22] conducted a retrospective study on T-ALL patients, 32 AYA patients treated with a DFCP. Ninety-three percent of the patients achieved CR with 3-year relapse-free survival and OS 88% and 83% respectively. Besides, DeAngelo et al. [23] enrolled 92 patients (18–50 years) for a median follow-up period (4.5 years). Eighty-five percent achieved CR, with 4-year EFS and OS 69% and 67% respectively.
Lastly, Alabdulwahab et al. [24] enrolled 38 patients with a median age (19 years) or a median follow-up period (22 months). Then, 92.1% achieved CR, with 1- and 3-year EFS were 80% and 68%, respectively, and 1- and 3-year OS were 88% and 72%, respectively.
As ALL therapies have more intensified, more toxicities have been increased especially in AYA patients. The toxicities of intensified protocols increase in both incidence and severity due to hormonal changes, body weight changes, and different chemotherapy metabolism [25]. Researchers are focused on decreasing early and late toxicities by good use of supportive care to improve OS [26].
Pancreatitis and venous thromboembolism are usually linked with l-asparaginase use in DFCP but may be related to increased steroid dose and the use of dexamethasone [27, 28]. Avascular necrosis incidence was more experienced in DFCP trials using dexamethasone [29]. Hyperglycemia risk is more likely in the AYA patients of ALL due to adult hormonal changes, and is usually associated with immune suppression and the risk for infections [30].
In our study, all patients (100%) had developed side effects. Neutropenia was the most common adverse event observed in 100% of the patients. Many other adverse events were also developed in patients under DFCP in the form of thrombocytopenia (70.73%), febrile neutropenia (68.29%), infections (24.39%), hyperglycemia (24.39%), mucositis (21.95%), venous thromboembolism (9.76%), neuropathy (9.76%), hepatotoxicity (9.76%), pancreatitis (7.31%), and avascular necrosis (7.31%). No patient developed an allergy.
These results match with a great extent with some differences that were reported in many studies. DeAngelo et al. [20] shown in their study that the incidence of venous thromboembolism (19%) and pancreatitis (13%) but this drug-related toxicity was controllable.
DeAngelo et al. [23] demonstrated toxicities of DFCP included thrombocytopenia (82%), hepatic toxicity (62%), infection (61%), hyperglycemia (45%), febrile neutropenia (33%), thrombosis (17%), pancreatitis (11%), stomatitis (11%), bone fractures (8%), osteonecrosis (5%), allergy (5%), and CNS complications (5%).
Alabdulwahab et al. [24] demonstrated toxicities of DFCP included febrile neutropenia (100%), sepsis (29%), pneumonia (26%), typhlitis (21%), myopathy (13%), pancreatitis (13%), osteonecrosis (7.8%), neurological toxicity (5%), and severe liver failure together with renal failure (2.6%). There was no venous thromboembolism was recorded apart from (7%) who had central catheter-related thrombosis.
The discrepancy between results of our study and other previous studies could be explained by variations in number and age of patients, follow-up time, ALL phenotype (B or T), Philadelphia chromosome incidence, the occurrence of favorable, and unfavorable chromosomal abnormalities, ethnic differences, and regimens of chemotherapy used as DFCP has many modifications. To our knowledge, this is the first study to collect data from Egyptian ALL patients. The present study had some limitations such as a small number of patients and a short time of follow-up. Also, our study was retrospective; therefore, unrecognized biases might be considered. To overcome these limitations, further larger, longer, prospective, and multicenter studies are necessary.