Philadelphia chromosome positive acute lymphoblastic leukemia

Positivity in adults with ALL associated with a 5-year survival rate of less than 10%.

The PH Chromosome abnormality is rare in children with ALL with an incidence of 2 to 5%.

PH positivity however represents the most common genetic sub group in ALL in adults with an overall incidence of 20 to 25%.

PH positive incidence in ALL increases with age and accounts for more than 50% of ALL in patients who are older than 50.

The presence of BCR-ABL rearrangement is the worst prognostic factor for ALL.

Children with positivity of Philadelphia chromosome in ALL treated with chemotherapy have survival rates of 25-30% and worse outcomes with WBC counts greater than 100,000.

Long-term survival of patients with Philadelphia chromosome positive ALL treated with imatinib and intensive chemotherapy have improved event free survival compared with historical controls treated without imatinib and comparable to patients treated with allogeneic stem cell transplant: five year disease free survival around 70%.

Prior to the introduction of tyrosine kinase inhibitors (TKIs) the response to chemotherapy was limited and the survival rate for patients with adult PH positive ALL was in the range of 10 to 20%.

Combination of TKI with chemotherapy is up to five years survival rate of 75% with third generation TKI(Ponatinib).

The bispecific monoclonal antibody blinatumomab targets two antigens, CD19 an antigen present in virtually all B lineage ALL cases, and CD3, which is present in all T lymphocytes.

The combination of TKIs  and blinatumomab lead to very high response rates of as high is 98% with 29% molecular responses.

Blinatumomab and inotuzumab are approved for management of relapsed Philadelphia chromosome positive ALL.

Promising results obtained with chemotherapy free regimens of Blinatumomab plus TKIs question the role of allogeneic stem cell transplant in first remission,  as patients treated with these agents achieve early and deep molecular responses and have excellent long-term outcomes.

TKIs have the ability to target and inhibit the auto phosphorylation caused by the BCR-ABL 1 kinase protein.

The use of TKI plus blinatumomab combinations most patients with Philadelphia chromosome positive ALL may be able to avoid hematopoetic stem cell transplant and chemotherapy.

Tisagenlecleucel CAR T cell therapy is a third line therapy for recurrent disease.

MRD plays a key role in prognosis and treatment decisions.




Leave a Reply

Your email address will not be published. Required fields are marked *