Philadelphia Positive Acute Lymphoblastic Leukemia (Ph+ ALL), Tawam Experience
Authors: Alam Arif , al Qawasmeh Khaled , Kanbar Jihad , Syed Masood H , Lal Amar , Hussain Sabir , Osman Hani Y , Kristensen Jorgen 
Published: November 2019

Acute lymphoblastic leukemia (ALL) is a relatively rare lymphoid disorder with approximately 11 cases per million persons per year in United States. It is seen more commonly in children however adults are also affected with the median age approximately 39 years. The prognosis is influenced by the age of the patient and genetic findings. Abnormal cytogenetic is present in approximately 80 % of the patients.

Philadelphia chromosome t (9;22) is seen in approximately 30 % of adult patients (Ph + ALL) and imparts a poor prognosis. Allogeneic stem cell transplant remains one of the corner stones of therapy along with Tyrosine Kinase Inhibitors TKIs (Imatinib or Dasatinib). Patients who are unable to go for transplant are kept on TKIs and continue consolidation and maintenance chemotherapy.

In this retrospective review, we present patients with Philadelphia chromosome positive ALL seen at our institute and their outcomes. Tumor registry data base was searched for adult patients with ALL between January 1st 2010 and June 30th 2015. Forty patients were identified with B cell ALL and ten patients were diagnosed with Ph+ ALL (25 % of the cohort). The median age was 30 years (range 18 - 73 years). Male to female ratio was 4.5:1

Induction therapy was given based on UK ALL protocol. Tyrosine kinase inhibitor (Imatinib) was added when information regarding BCR-ABL translocation status was available. Interestingly 8 out of the 10 Ph+ patients also had CD 20 positive disease and were treated with rituximab in addition to standard chemotherapy and TKI.

Two patients were lost from follow-up after receiving initial therapy and achieving remission. Four patients had HLA identical siblings and were able to go for allogeneic stem cell transplant. With a median follow up of 28 months (range 1 to 57 months), 3 of the 4 patients are alive and in complete molecular remission. One patient relapsed 19 months post-transplant and died of complications of a 2nd transplant. The remaining 4 patients were unable to go for allogeneic stem cell transplant. They were treated with Hyper-CVAD regimen and Dasatinib (Rituximab was used in patients with CD 20 positive clone). One patient died of colitis and relapsed ALL (36 months post diagnosis) while the other 3 patients are alive and on active therapy, all being in complete molecular remission.

Discussion:

This is the first report of incidence, management and outcome of Ph+ ALL from UAE. Ph + ALL contribute to 25 % of the cohort of ALL patients in our center. Majority of this cohort was also CD 20 positive. All patients achieved a complete hematologic remission after induction therapy. However, less than half of the patients were able to go for allogeneic stem cell transplantation as consolidation due to different reasons. Post transplantation use of TKI remains variable.

HyperCVAD and Dasatinib appears to be a reasonable but toxic alternative for patients who are unable to go for allogeneic stem cell transplantation with a reported estimated survival of 64 % at 2 years interval.

Disclosures

No relevant conflicts of interest to declare.