Updated NCCN guidelines for acute lymphoblastic leukemia.

These guidelines aimed to update treatment options for patients with Philadelphia chromosome-positive (Ph+) and negative (Ph-) acute lymphoblastic leukemia (ALL).

Acute lymphoblastic leukemia (ALL) represents 75% to 80% of acute leukemia among children and so is the most common form of childhood leukemia. It represents only 20% of all leukemias among adults. Approximately 25% of patients with ALL have Ph+ ALL. This subtype of ALL contains an abnormal BCR-ABL gene. This abnormal gene makes an abnormal protein that helps leukemia cells to grow.

The cure rates and survival outcomes of patients with ALL have improved dramatically in recent times, especially in children. This is due to advances in treatments. This National Comprehensive Cancer Network (NCCN) has provided an update on the treatment options for patients with ALL.  

Ph+ ALL is rare in children. In adolescents and young adults (AYAs) with ALL, the standard therapy used to be hematopoietic stem cell transplant (HSCT). This involves transplanting healthy stem cells to replace the ones destroyed by anti-cancer therapy. However, in recent years, targeted therapies that block the abnormal BCR-ABL gene have been developed. These are called BCR-ABL-targeted tyrosine kinase inhibitors (TKIs) such as imatinib (Gleevec), dasatinib (Sprycel), and ponatinib (Iclusig).  

Chemotherapy combined with TKIs like imatinib or dasatinib provides good outcomes for Ph+ ALL patients. Imatinib (or other TKIs) combined with hyper-CVAD (cyclophosphamide, vincristine, doxorubicin, dexamethasone) and HSCT also showed good results for Ph+ ALL patients.   

In patients with relapsed or refractory (r/r) Ph+ ALL treatment is challenging. For patients who relapse after HSCT, donor lymphocyte infusion (DLI) combined with newer TKIs like dasatinib and nilotinib (Tasigna) may be useful.  

For patients who have resistance/relapse to imatinib (1st generation TKI), second and third-generation TKIs like dasatinib, nilotinib, bosutinib (Bosulif), or ponatinib can be used. Other approved options for r/r Ph+ ALL are immunotherapies blinatumomab (Blincyto) or inotuzumab ozogamicin (InO; Besponsa).  

Chimeric antigen receptor (CAR) T-cell therapy is currently is the only cure for r/r ALL. This involves taking T cells (a type of immune cell) and changing them into the lab so they can fight and kill cancer cells. However, many patients are not eligible for CAR T-cell therapy. 

Management of Ph- ALL involves autologous HSCT (healthy cells transplanted from the patients themselves) has same outcomes as chemotherapy alone in patients with Ph- ALL. For high-risk cases in first complete remission, autologous HSCT can be used. Allogeneic HSCT (cells transplanted from a donor) is beneficial for standard risk patients with Ph- ALL but has no significant advantage for high-risk patients.  

As well as being approved for use in Ph+ ALL, blinatumomab can be used in the treatment of Ph- ALL. It can eradicate persistent minimal residual disease (MRD; the few cancer cells left behind after treatment) following chemotherapy. 

Chemotherapy regimens such as the Linker-4 drug regimen (vincristine, daunorubicin, prednisone, and asparaginase) or Hyper-CVAD with or without rituximab (Rituxan) can also be used for Ph- ALL. 

In patients with r/r Ph- ALL, HSCT is the only potentially curative option. Blinatumomab can be used for treatment of relapsed Ph- ALL. However, it has significant side effects which need to be monitored.  

Nelarabine (Arranon) is a chemotherapy approved for T-ALL that has relapsed after at least two lines of chemotherapy. There is limited data for relapsed Ph- ALL but it may be an option.  

Augmented Hyper-CVAD (asparaginase, intensified vincristine, and intensified dexamethasone) is a potential treatment option for patients with relapsed Ph- ALL. 

Clofarabine (Clolar) is approved for treatment of pediatric patients with ALL that is r/r and has been treated with two prior regimens. It may be used in the treatment of r/r Ph- ALL 

The MOpAD regimen (methotrexate, vincristine, PEG-L-asparaginase, and dexamethasone) can be considered in patients with Ph- ALL who have received the maximum dose of anthracycline, have heart problems and are relatively unfit. 

Vincristine sulfate liposomal injection (VSLI) has been approved for use in patients with Ph- ALL who are in their second or greater relapse. 

These guidelines aimed to update treatment options for patients with ALL.