Clinical and prognostic significance of the Philadelphia chromosome in adult patients with acute lymphoblastic leukemia

Abstract

Between 1983 and 1991 the Philadelphia chromosome (Ph1) was found in bone marrow and/or peripheral blood cells of 25 adult patients with acute lymphoblastic leukemia (ALL). The Ph1 as sole anomaly was seen in 13 patients, while six patients had additional structural and another six structural and numerical aberrations. Most patients (23/25) received combination chemotherapy according to the BMFT protocols 1/81, 2/84, 3/87, and 4/89. For 25 evaluable patients two early deaths, two treatment failures, two partial remissions (PR), and 19 complete remissions (CR) after phase 1 or 2 of the induction regimen were recorded. Two of these 19 patients who achieved CR are presently disease free, whereas 17 have relapsed after a median duration of remission of 9 months. Actuarial median survival for all patients was 13 months. The probability of continuous complete remission (CCR) after 39 months, as well as that of survival after 40 months, is only 6%. Our results confirm that the presence of the Ph1 is associated with a poor prognosis in adult-ALL patients. Therefore, whenever first CR is obtained and an HLA-identical donor is available, allogeneic bone marrow transplantation (BMT) should be performed at once, the more so, since transplantation in second CR seems to offer no cure. Future studies will have to show whether an intensified cytotoxic therapy can improve the prognosis of Ph1(+)-ALL.

Allogeneic bone marrow transplantation vs chemotherapy for children with Philadelphia chromosome-positive acute lymphoblastic leukemia

“…The presence of the Ph chromosome is an independent adverse prognostic factor characterized by a poor response to chemotherapy, short remission duration and poor likelihood of survival. [1][2][3][4][5] Although conventional chemotherapy can induce remission in 50-70% of patients, chemotherapy fails to maintain durable complete remission (CR) and produces an overall survival of 6-20%. 1,2,5 Similarly, the approach of augmented post-induction chemotherapy, including high-dose chemotherapy with or without autologous stem-cell rescue has failed to improve the outcomes for patients who have this disease.…”

“…[1][2][3][4][5] Although conventional chemotherapy can induce remission in 50-70% of patients, chemotherapy fails to maintain durable complete remission (CR) and produces an overall survival of 6-20%. 1,2,5 Similarly, the approach of augmented post-induction chemotherapy, including high-dose chemotherapy with or without autologous stem-cell rescue has failed to improve the outcomes for patients who have this disease. [2][3][4]6 Myeloablative chemotherapy followed by haematopoietic stem-cell rescue from an allogeneic donor in CR1 has been shown to cure 20-75% of patients.…”

Final report of a phase II study of imatinib mesylate with hyper-CVAD for the front-line treatment of adult patients with Philadelphia chromosome-positive acute lymphoblastic leukemia

“…However, the responses were short-lived with long-term survival rates of less than 20%. 2,[5][6][7][8] Slow and partial reduction of the leukemic clone by traditional cytotoxic chemotherapy may be responsible for the poor prognosis associated with Ph + ALL when compared with less aggressive variants of ALL. 9 Heretofore, allogeneic stem cell transplant (ASCT) in first remission was the only effective curative option, and was offered to all patients in first remission who had a suitable donor.…”

High rate of chromosome abnormalities detected by fluorescence in situ hybridization using BCR and ABL probes in adult acute lymphoblastic leukemia

“…1,[3][4][5]12,[17][18][19] Therefore, the unambiguous identification of these patients is mandatory. Conventional chromosome analysis allows for unequivocal diagnosis of Ph-positive ALL if a standard Ph translocation t(9;22) is present.…”