Acute Myeloid and Chronic Myeloid Leukemia in Children

Dr. Danewa explained that upfront bone marrow transplant has no role in most pediatric leukemia. It is reserved for cases without morphological remission (blasts above 10% at the end of induction), for hypodiploidy (fewer than 44 chromosomes), or for relapse. For benign conditions, the leading indication, especially in Africa, is sickle cell disease, where earlier transplant, ideally before age 12 and before pain crises, stroke or chest syndrome accumulate, gives a better outcome. He described three transplant types: matched sibling, matched unrelated donor via registry, and haploidentical transplant from a parent, with haploidentical success running around 70 to 80% depending on the underlying disease.

Yes. Dr. Danewa confirmed bone marrow transplant is a cure for sickle cell disease, and that outcomes are best the earlier it is done, since delay allows organ damage and comorbidities to accumulate and lowers the chance of success.

In relapsed or refractory leukemia, where prior treatment options offered only a 5 to 10% chance of success, both Western data and four to five years of follow-up on India's own indigenous CAR T-cell programs are now showing 50 to 60% success.

Dr. Danewa explained that CAR T-cell therapy targets surface antigens on the cancer cell itself, such as CD19 or CD22 in ALL: a patient's own T cells are removed, engineered to recognize that antigen, and returned to attack the cancer directly. Because cancer cells can develop antigen escape by losing one target, dual CAR T-cell therapy now targets CD19 and CD22 together, and similar antigen-targeted approaches (anti-GD2) are being developed for neuroblastoma and, increasingly, for brain tumors.

Only about 1% of pediatric tumors are familial or have an identifiable genetic cause. Most arise from spontaneous mutations that the body's own immune checkpoints fail to catch. There is no equivalent of smoking or alcohol as a modifiable risk factor in children, and no established viral cause, so there is currently no basis for a preventive vaccine.

AML survival runs roughly 50 to 70%, against 80 to 90% for ALL. The gap is closing through better supportive care that reduces deaths from treatment toxicity and infection, and through improved access to haploidentical bone marrow transplant for children who relapse.

AML leukemia cells lack a clean, AML-specific surface target comparable to CD19 or CD22 in ALL, and are prone to shedding whatever target is identified. This is expected to change as the science evolves.

Gemtuzumab, directed at CD33, and venetoclax, now available in generic form, are used in refractory disease. Children whose genetics show an FLT3 mutation have access to first, second or third-generation FLT3 inhibitor tablets, used either to help achieve remission or as maintenance after transplant to prevent relapse.

In its chronic phase, CML can be managed entirely with oral tablets on an outpatient basis, starting with imatinib, with periodic monitoring to judge when a switch to a later-generation drug such as dasatinib, nilotinib, ponatinib or asciminib is warranted.

It is rare. One pediatric center sees only three or four pediatric CML cases a year.