How is Philadelphia chromosome (Ph)-positive acute lymphoblastic leukemia (ALL) treated?

Updated: Jul 02, 2021
  • Author: Karen Seiter, MD; Chief Editor: Matthew C Foster, MD  more...
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Answer

Answer

In the past, the prognosis for patients with Ph+ ALL was very poor. However, advances (eg, treatment that includes TKIs) have brought about an improved outcome for this subtype of ALL. 

Use of high-dose cytarabine induction regimens has resulted in a higher complete remission rate than that seen with traditional ALL regimens. For example, using ALL-2 induction (cytarabine 3 g/m2 IV over 3h daily for 5 d and mitoxantrone 80 mg/m2 on day 2), patients with Ph+ ALL obtain a rapid hematologic, cytogenetic, and molecular remission [6]

Ph+ ALL is characterized by the BCR-ABL fusion (usually p190), which is a target of several TKIs. Currently, imatinib, dasatinib, and ponatinib are TKIs approved by the FDA for treatment of Ph+ ALL. Although these TKIs have activity as single agents, they are best used in combination with multiagent chemotherapy regimens. [7, 8, 9, 10]  For example, the addition of imatinib (600 mg PO daily) to hyper-CVAD increased the 3-y rate of complete remission duration to 68%, compared with 24% of patients treated with hyper-CVAD without imatinib [10]

Likewise, the addition of dasatinib (140 mg PO daily) to hyper-CVAD resulted in complete remissions in 94% of patients. [11] After a median follow-up of 14 mo, the median disease-free survival had not been reached.

Ponatinib has shown a 41% major hematologic response in Ph+ ALL after failure or intolerance of dasatinib or nilotinib, including in patients with the T315I mutation. [12] Because ponatinib carries a high risk for thromboembolic events, its use is limited to patients with T315I-positive, Ph+ ALL for whom no other TKI therapy is indicated. [13]


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