Detection of Philadelphia chromosome-positive acute lymphoblastic leukemia by polymerase chain reaction: possible eradication of minimal residual disease by marrow transplantation

Abstract

Minimal residual disease (MRD) in patients with Philadelphia chromosome- positive acute lymphoblastic leukemia (Ph1 ALL) who received allogeneic (n = 9) or autologous (n = 6) bone marrow transplantation (BMT) was evaluated by the polymerase chain reaction (PCR) for the bcr-abl transcript. Twelve patients received BMT at the time of hematologic and cytogenetic remission. However, MRD was detected in 8 of 10 patients evaluated. Seven patients, including three who had MRD before BMT, continue to have a disease-free survival 5 to 64 months after BMT. Twenty-one specimens obtained from these patients at various times after BMT did not show MRD. In three patients, MRD detected just before BMT seems to be eradicated by BMT protocol. The other eight patients developed cytogenetic or hematologic relapses 2 to 8 months after BMT. Seven of 14 samples from these patients demonstrated MRD, which preceded clinical relapse by 3 to 9 weeks. Thus, this technique for the detection of MRD appears to be useful for the more precise assessment of various antileukemia therapies and for early detection of leukemia recurrence.

Prospective monitoring of BCR‐ABL1 transcript levels in patients with Philadelphia chromosome‐positive acute lymphoblastic leukaemia undergoing imatinib‐combined chemotherapy

“…Another important finding of this study was the significant relationship between MRD elevation and relapse. This finding is in accordance with those of several studies published in the 1990s in which the conversion from negative to positive RT-PCR results was associated with subsequent relapse in Ph+ ALL patients (Miyamura et al, 1992;Preudhomme et al, 1997;Radich et al, 1997;Mitterbauer et al, 1999). Our results suggest that an increase in the MRD level at a single time point is predictive of subsequent relapse, but such patients can be successfully treated with allogeneic HSCT.…”

Impact of tyrosine kinase inhibitors on patient outcomes in Philadelphia chromosome‐positive acute lymphoblastic leukaemia

“…The presence of molecular MRD among patients with Ph+ ALL who have received HSCT is also associated with early relapse (Miyamura et al , 1992; Preudhomme et al , 1997; Radich et al , 1997; Stirewalt et al , 2003). MRD is normally monitored by reverse transcription polymerase chain reaction (RT‐PCR) analysis of BCR‐ABL1 transcript levels in bone marrow or peripheral blood, although one group has reported that blood monitoring may have lower sensitivity (Preudhomme et al , 1997).…”

Utilization of polymerase chain reaction technology in the detection of solid tumors

“…Chromosomal translocations generally have a high degree of concordance with specific leukemias and lymphomas, as seen with t(9;22) (Philadelphia chromosome) in chronic myeloid leukemia (CML), t(15;17) in acute promyelocytic leukemia, and t(14;18) (q24;q21) in non‐Hodgkin's lymphoma 22‐28. Translocations are frequent in cells of lymphoid or myeloid origin, as gene rearrangements of the T‐cell receptor or immunoglobulins are common in these cells.…”