Treatment approaches in pediatric and adolescent and young adult acute lymphoblastic leukemia by representative protocols
| . | Pediatric protocol for ALL* . | Pediatric-inspired ALL protocol for AYAs . | Adult ALL protocol for AYAs . |
|---|---|---|---|
| Representative protocol used | AALL1732†,37 | CALG B10403‡,2 | Hyper-CVAD38,39 |
| Induction chemotherapy agents used | DXM (<10 years old)/PDN (≥10 years old) VCR DNR ASP | PDN VCR DNR ASP | Hyperfractionated CPM VCR DOX DXM HD-MTX ARAC ±Rituximab if CD20+ |
| Approach to CNS prophylaxis | IT ARAC at diagnosis, then IT MTX throughout treatment 18 Gy CRT only if CNS3 | IT ARAC at diagnosis, then IT MTX throughout treatment Prophylactic CRT in any patient with T-ALL 18 Gy CRT if CNS leukemia at diagnosis | Alternating IT MTX and IT ARAC in induction and consolidation 30 Gy CRT to whole brain (frank leukemia) or to skull base (cranial nerve involvement) |
| Use of HSCT | EOC MRD >0.01 | If persistent MRD at EOI; if high-risk cytogenetics in CR1 | If persistent MRD at EOI; if high-risk cytogenetics in CR1 |
| Immunotherapy | InO given postconsolidation in experimental arm | Not used | Rituximab if CD20+ |
| Key regimen differences compared to a pediatric protocol | — | Extended remission induction (PDN, DNR, VCR, ASP) One IM phase (uses escalating-dose MTX) while pediatric protocol has 2 IM phases (HD-MTX, then escalating-dose MTX) Patients with T-ALL who were CNS negative at presentation receive prophylactic CRT, which is not done in pediatric protocols for most patients with T-ALL More likely to proceed to HSCT Does not use novel immunotherapy agents | ASP not used in induction Less frequent and less aggressive IT CNS prophylaxis Higher doses of myelosuppressive drugs More likely to proceed to HSCT Use of rituximab if CD20+ |
| . | Pediatric protocol for ALL* . | Pediatric-inspired ALL protocol for AYAs . | Adult ALL protocol for AYAs . |
|---|---|---|---|
| Representative protocol used | AALL1732†,37 | CALG B10403‡,2 | Hyper-CVAD38,39 |
| Induction chemotherapy agents used | DXM (<10 years old)/PDN (≥10 years old) VCR DNR ASP | PDN VCR DNR ASP | Hyperfractionated CPM VCR DOX DXM HD-MTX ARAC ±Rituximab if CD20+ |
| Approach to CNS prophylaxis | IT ARAC at diagnosis, then IT MTX throughout treatment 18 Gy CRT only if CNS3 | IT ARAC at diagnosis, then IT MTX throughout treatment Prophylactic CRT in any patient with T-ALL 18 Gy CRT if CNS leukemia at diagnosis | Alternating IT MTX and IT ARAC in induction and consolidation 30 Gy CRT to whole brain (frank leukemia) or to skull base (cranial nerve involvement) |
| Use of HSCT | EOC MRD >0.01 | If persistent MRD at EOI; if high-risk cytogenetics in CR1 | If persistent MRD at EOI; if high-risk cytogenetics in CR1 |
| Immunotherapy | InO given postconsolidation in experimental arm | Not used | Rituximab if CD20+ |
| Key regimen differences compared to a pediatric protocol | — | Extended remission induction (PDN, DNR, VCR, ASP) One IM phase (uses escalating-dose MTX) while pediatric protocol has 2 IM phases (HD-MTX, then escalating-dose MTX) Patients with T-ALL who were CNS negative at presentation receive prophylactic CRT, which is not done in pediatric protocols for most patients with T-ALL More likely to proceed to HSCT Does not use novel immunotherapy agents | ASP not used in induction Less frequent and less aggressive IT CNS prophylaxis Higher doses of myelosuppressive drugs More likely to proceed to HSCT Use of rituximab if CD20+ |
Protocols described are for Philadelphia chromosome-negative acute lymphoblastic leukemia.
ARAC, cytarabine; ASP, asparaginase; CNS, central nervous system; CPM, cyclophosphamide; CR1, first complete remission; CRT, cranial radiation therapy; CVAD, cyclophosphamide, vincristine sulfate, doxorubicin hydrochloride, dexamethasone; DNR, daunorubicin; DOX, doxorubicin; DXM, dexamethasone; EOC, end of consolidation; EOI, end of induction; Gy, Gray; HD, high dose; HSCT, hematopoietic stem cell transplant; IM, interim maintenance; InO, inotuzumab ozogamicin; IT, intrathecal; MTX, methotrexate; PDN, prednisone; VCR, vincristine.
A high-risk pediatric protocol is used as the representative pediatric regimen, as adolescents treated on pediatric protocols are considered high risk at time of diagnosis due to age.
COG trial AALL1732 was selected for use in this table for the high-risk pediatric protocol as this is the current ongoing pediatric trial in the COG. CALGB 10403 is based on the COG trial AALL0232 control arm.40 AALL0232 included 2 randomizations (dexamethasone vs prednisone for induction steroids and high-dose MTX vs Capizzi MTX in IM 1) while AALL1732 uses dexamethasone in induction if <10 years of age and prednisone in induction if ≥10 years of age, high-dose MTX in IM 1 with Capizzi MTX in IM 2, and randomization of the novel agent InO.37,40
Protocol CALGB 10403 was selected for the pediatric-inspired representative regimen for adult ALL as this is the trial discussed throughout the article. Current ongoing Alliance (formerly CALGB) trial A041501 is also testing the novel agent InO.