Philadelphia Positive Acute Lymphoblastic Leukemia (Ph+ ALL), Tawam Experience

Abstract

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.

Current Status and Management of Chronic Myeloid Leukemia in the Gulf Region: Survey Results and Expert Opinion

“…Alam et al reported real-world data from six patients in Tawam Hospital, UAE, who were on TKI therapy for 11 years and had undetectable levels of BCR-ABL1 transcript for more than 2 years. Following a trial of TFR, half of the patients reached the six-month milestone: two remained at undetectable levels, one patient had MR4.49, and none of the patients experienced TKI withdrawal syndrome [17]. Another study at the Kuwait Cancer Control Center analyzed data from 42 patients who had a trial of TFR.…”

Skuteczne leczenie ratunkowe inhibitorami kinaz tyrozynowych chorego na B-komórkową ostrą białaczkę limfoblastyczną Filadelfia-dodatnią

“…Optymalnym leczeniem była polichemioterapia jak w innych ALL; po uzyskaniu całkowitej remisji (CR) u chorych w dobrym stanie z dobranym dawcą szpiku zalecano przeszczepienie allogenicznych krwiotwórczych komórek macierzystych (allo-HSCT, allogeneic hematopoietic stem cell transplantation), co istotnie poprawiło wyniki leczenia [1,2]. Istotną poprawę rokowania w tej grupie chorych przyniosło zastosowanie TKI w połączeniu z chemioterapią [3][4][5]. Początkowo stosowano jedynie imatynib, w ostatnich latach wykazano jednak, że TKI drugiej i trzeciej generacji powodują szybszą i głębszą remisję białaczki [6][7][8][9][10].…”

Combined inhibition of BCR-ABL1 and the proteasome as a potential novel therapeutic approach in BCR-ABL positive acute lymphoblastic leukemia

“…In 80% of patients with ALL, genetic aberrations can be found in the leukemic cells [ 2 , 3 ], the most common lesion being the Philadelphia chromosome with its translocation t(9;22) accountable consecutively for the most common genetically defined subtype of adult ALL. Between 20 to 30% of all adult ALL patients and more than 50% of patients in the age group above 60 years carry this lesion associated with a dismal prognosis [ 4 , 5 ].…”