Abstract Ref Number = APCP65
Relapse!!! How to avoid, diagnose and treat relapse in acute lymphoblastic leukaemia (ALL)
VivaGoh Foundation AProf in Paediatric Oncology, National University of Singapore
Head, VivaUniversity Childrens Cancer Centre, National University Hospital
Relapse (kambul balik) means return of cancer after achieving initial response to treatment, is a feared word among doctors, nurses, patients and families. This is especially important because relapsed cancer is often more resistant and usually means toxic treatment, lot of suffering and eventual death. In Indonesia and LMICs, after newly diagnosed ALL, relapse from ALL is probably the second most common type of cancer in children.
The best way to avoid a relapse is to give the best treatment we can afford when ALL is first diagnosed. Because ALL is uncommon but curable, all newly diagnosed ALL patients should be referred to hospital with good experience managing childhood ALL. This means that governments should designate national centres to treat ALL when expertise to diagnosis and treat ALL is done. For example, in Myanmar, ALL is treated in Yangon Children’s and Mandalay Children’s Hospital. In Vietnam, there are 7 national centres that treat childhood ALL.
Not all relapse ALL means carry the same bad outcome. The prognosis depends on
1. time-to-relapse. Early relapse within 6 months of stopping therapy is bad. Relapse after 2 years of stopping therapy can be treated with repeat high risk chemotherapy.
2. Site-of relapse – relapse in the bone marrow is bad, relapse in CNS and testes may be salvageable with repeat chemotherapy and radiotherapy.
3. Genetics of the ALL – favourable cytogenetics like hyperdiploid ALL and ETV6-RUNX1 do better than Hypodiploid ALL, MLL-rearrangement.
4. Type of treatment received for front line chemotherapy. Patients relapsing after more intensive chemotherapy or bone marrow transplants are more difficult to salvage than those relapsing from lower intensity therapy.
Remember that relapse carries a poor outcome and very toxic therapy. So one must be completely certain of the relapse. For LMIC, this means the patient should have clear symptoms of relapse like high blast count in the peripheral blood, severe anaemia, severe thrombocytopaenia. There must be clear histological diagnosis of relapse – either bone marrow blasts >30% consistently, CSF WBC >100 or presence of masses in the brain or testicular biopsy proven relapse. If in doubt, patient should be referred to a centre with experience with diagnosis of ALL relapse. Flow cytometry of CD19+/CD10+ blasts alone is insufficient to diagnose relapse as haematogones have the same flow cytometry features.
Relapse treatment is often more intensive but patients are weaker and at high risk of dying. Again relapse therapy should be done in the best affordable centre in the country. Bone marrow transplantation is not available in many LMIC like Indonesia, Philippines and Bangladesh. Often referral to another country or national transplant centre is needed. Use of mono-clonal antibodies like blinatumomab and inotuzumab can achieve a transient second remission for bone marrow transplantation. Recently immunotherapy using viral vectors to insert gene constructs with Chimeric Antigen Receptor into T-cell (CAR-T) cells against CD19 has successfully salvaged relapse resistant ALL. With targeted therapy, we are moving away from more toxic relapse therapy to test whether we can improve cure in relapsed ALL patients with less toxicity.