*4.1.4 Immunoglobulin heavy chain gene (IGH) rearrangement, CRLF2 overexpression*

*IGH*, a novel, adverse prognostic, cytogenetic driver is seen in less than 3% of pediatric and 10% of AYA ALL [74]. This rearrangement is characterized by the juxtaposition of a partner oncogene like *CRLF2* (25%) or *CEBP* (10%) with *IGH* that drives the overexpression. *CRLF2* overexpression is seen in a very high proportion (>50%) of children with DS, but the prognostic significance is still unclear [59].

#### *4.1.5 iAMP21*

This novel prognostic marker is seen in about 1.5–2% of pediatric ALL and is characterized by ≥3 extra copies of *RUNX1* gene on a single abnormal chromosome 21q22 [75, 76]. Increased predisposition to develop *iAMP21* ALL is seen in carriers of the Robertsonian translocation involving chromosomes 15 and 21 [77]. This subtype presents in older children (median 10 years), is more common in females, and presents with WBC count of less than 50 × 10<sup>9</sup> /L. Presence of this mutation confers a poor prognosis with standard therapy as well as high post remission-induction MRD [41, 78, 79]. However, the outcomes are better with MRD-guided and intensive chemotherapy, as shown in the UKALL2003 and the ALL-BFM 2000 studies, hence precluding the need for SCT in first remission [41, 42].

**37**

**Table 1.**

*Research Council (United Kingdom).*

*Pediatric Acute Lymphoblastic Leukemia: Recent Advances for a Promising Future*

AYA constitutes a unique group of ALL with an age range of 15–39 years as defined by the NCI. Based on disease biology, there has always been a debate as to the best regimen to be used in this age group. Historically, ALL in the AYA population has been associated with a poor outcome and higher treatment related morbidity. However, the current focus of treating AYA as per pediatric protocols has resulted in improvement in their outcomes [14, 15] as shown in **Table 1**. Chemotherapy protocols similar to the BFM backbone with corticosteroids, vincristine and asparaginase in induction, post-remission asparaginase, and CNS prophylaxis during induction have shown improved survival in this cohort of patients. Also, SCT is offered only to the very-high risk population in first complete

To support this further, the excellent results from the large study by the GRAALL group have shown significantly improved survival (66% vs. 44%, P < 0.001) for those treated with pediatric-inspired protocols compared to historical controls treated with adult protocols [81]. The largest study which has evaluated this hypothesis is the US intergroup trial C10403, in which 318 AYA patients were treated as per the standard arm of the COG AALL0232 protocol. Encouraging results from this study showed a 2-year event free survival (EFS) of 66% and overall survival (OS) of 78%, with manageable toxicity profile and subsequently the NCI recommended that pediatric-inspired protocols could be used effectively up to

This high-risk group of ALL constitutes about 20–30% of the adult ALL and 3% of pediatric ALL [88]. Approximately 90% of the pediatric Ph + ALL have the p190 translocation, which results from the translocation within the 'minor' breakpoint cluster region (mBCR) [89]. It is also characterized by a high frequency (66%) of deletions in B-cell development genes like IKZF1, PAX5, EBF1 and CDKN2A/B. [33, 88, 90]. Historically, outcomes were extremely poor with 5-year OS of 19%

**Serial no. Study group Patients numbers (n) Median age (y) Survival (%)** 1. CCG [14] 197 16 67, OS 7y 2. CALGB [15] 124 19 46 3. FRALLE93 [15] 77 16 67 EFS 4. AIEOP [83, 84] 150 15 80, OS 2y 5. DCOG [85] 47 12 71 EFS 6. NOPHO92 [86] 36 16 74, OS 5y 7. MRC ALL [87] 61 15–17 71, OS 5y 8. UKALL2003 [24] 229 16–24 72 EFS *CCG, Children's Cancer Group; CALGB, Cancer and Leukemia Group; FRALLE, French Acute lymphoblastic Leukemia Study Group; AIEOP, Associazione Italiana di Ematologia e Oncologia Pediatrica; DCOG, Dutch Childhood Oncology Group; NOPHO, Nordic Society for Pediatric Hematology and Oncology; MRC ALL, Medical* 

*DOI: http://dx.doi.org/10.5772/intechopen.87092*

*4.2.1 Adolescents and young adults (AYA) with ALL*

*4.2.2 Philadelphia-chromosome positive ALL (Ph + ALL)*

*Improved outcomes for AYA when treated according to pediatric-based protocols.*

**4.2 Treatment**

remission (CR1) [80].

the age of 40 years [82].
