Outcome of treatment in adults with Philadelphia chromosome-positive and/or BCR–ABL-positive acute lymphoblastic leukemia—retrospective analysis of Polish Adult Leukemia Group (PALG)

Abstract

Patients with Philadelphia chromosome-positive (Ph+) and/or BCR-ABL+ acute lymphoblastic leukemia (ALL) have extremely poor prognoses. Most of these patients have additional, heterogenous karyotype abnormalities, the majority of which have uncertain clinical significance. In this study we analyzed the clinical characteristics, karyotype abnormalities, and outcome of 77 patients with Ph+ and/or BCR-ABL+ ALL registered in Poland in 1997-2004. In 31/55 patients with known karyotype, the sole t(9;22)(q34;q11) abnormality had been diagnosed; in one patient, variant translocation t(4;9;22)(q21q31.1;q34;q11), and additional abnormalities in 23 (42%) patients, had been diagnosed. The characteristics of the patients with Ph chromosome and additional abnormalities were not significantly different when compared with the entire analyzed group. Out of 77 patients, 54 (70%) achieved first complete remission (CR1) after one or more induction cycles. The overall survival (OS) probability of 2 years was 63, 43, and 17% for patients treated with allogeneic stem cell transplantation (alloSCT), autologous SCT, and chemotherapy, respectively (log rank p=0.002). Median OS from the time of alloSCT was significantly longer for patients transplanted in CR1 compared with alloSCT in CR >1 (p=0.032). There were no significant differences in CR rate, disease-free survival (DFS), and OS for patients with t(9;22) and additional abnormalities compared with the whole group. Only WBC >20 G/l at diagnosis adversely influenced OS probability (log rank p=0.0017). In conclusion, our data confirm poor outcome of Ph+ and/or BCR-ABL+ ALL. Only patients who received alloSCT in CR1 had longer DFS and OS. We have shown that additional karyotype abnormalities did not influence the clinical characteristics of the patients; however, their influence on treatment results needs to be further assessed.

Prospective outcome data on 267 unselected adult patients with Philadelphia chromosome–positive acute lymphoblastic leukemia confirms superiority of allogeneic transplantation over chemotherapy in the pre-imatinib era: results from the International ALL Trial MRC UKALLXII/ECOG2993

“…These remission and survival figures are entirely consistent with previously published, smaller studies. 4,6,13 The factors predicting achievement of CR in our study were age and presenting WBC count.…”

Use of tyrosine kinase inhibitors to prevent relapse after allogeneic hematopoietic stem cell transplantation for patients with Philadelphia chromosome–positive acute lymphoblastic leukemia: A position statement of the Acute Leukemia Working Party of the European Society for Blood and Marrow Transplantation

“…Translocation (9;22) or the BCR‐ABL fusion gene is detected in approximately 5% to 15% of adolescents, in 25% to 30% of patients aged 25 to 35 years, and in more than 35% to 40% of patients older than 35 years . Historically, treatment results for Ph‐positive ALL were very poor, and a patient's prognosis was dismal . Although complete remission (CR) was obtained in 60% to 90% of patients after first‐line therapy, the relapse rate was very high, and the probability of long‐term survival did not exceed 10% in patients treated with standard chemotherapy and 30% to 35% in those undergoing allogeneic hematopoietic stem cell transplantation (alloHSCT) .…”

Poor outcomes associated with +der(22)t(9;22) and −9/9p in patients with Philadelphia chromosome‐positive acute lymphoblastic leukemia receiving chemotherapy plus a tyrosine kinase inhibitor

“…The presence of t(9;22) is the hallmark of Philadelphia chromosome‐positive (Ph+) acute lymphoblastic leukemia (ALL). Additional chromosomal abnormalities (ACAs) are also present at diagnosis in 40%‐70% of patients with Ph+ ALL . Prior to the routine use of tyrosine kinase inhibitors (TKIs), the presence of ACAs in Ph+ ALL was associated with worse outcomes in some but not all studies.…”

“…Additional chromosomal abnormalities (ACAs) are also present at diagnosis in 40%‐70% of patients with Ph+ ALL . Prior to the routine use of tyrosine kinase inhibitors (TKIs), the presence of ACAs in Ph+ ALL was associated with worse outcomes in some but not all studies. In small reports of patients treated with chemotherapy plus imatinib, ACAs have been associated with shorter relapse‐free survival (RFS) and overall survival (OS) .…”