Ph+ ALL is the most frequent genetic ALL subgroup in adults.
It counts for 25 t0 30% of all ALLs in adults overall and progressively more frequent with age.
Ph+ ALL His less common and young adults and accounts were approximately 50% of all a LL and adults older than 50 years.
Ph+ ALL is much rarer in children.
Ph+ ALL was the most lethal condition in hematology, until the introduction of TKIs.
Positivity in adults with ALL was 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%.
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).
Ponatinib is superior in efficacy and comparable in safety versus imatinib for frontline treatment of adults with newly diagnosed Philadelphia chromosome, positive ALL.
Ponatinib demonstrates superior MRD negative complete remission at the end of induction versus imatinib when combined with reduced intensity, chemotherapy in adults with newly diagnosed filled for Philadelphia positive ALL (PhALLCON).
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.