Clinical course and serial monitoring of PML-RARα NQs derived from bone marrow and/or peripheral blood by real-time quantitative RT-PCR in 2 patients treated on protocol INT0129.
(A) Patient 1 received induction treatment with daunorubicin plus cytarabine (DA) and, after 2 courses of DA consolidation chemotherapy, received all-trans retinoic acid (ATRA) maintenance therapy for 1 year. (B) Patient 2 received remission induction treatment with ATRA and, after 2 courses of DA consolidation chemotherapy, received no further treatment. Both patients are in continuing clinical remission after longer than 5 years follow-up. The monitoring intervals designated on the abscissa are representational and not time-linear. PML-RARα NQs, indicated on the left ordinate, were determined by dividing PML-RARα copy number by GAPDH copy number. Bone marrow NQs, stippled columns; peripheral blood NQs, hatched columns. Assay sensitivity is represented by the reciprocal of the GAPDH copy number (1 divided by the GAPDH copy number), indicated on the right ordinate. The sensitivity cutoff at 1/2.5 × 105 GAPDH copies corresponds to a sensitivity detection level of 104.17 Thus, the further below the cutoff line, the more sensitive the assay, while values above the line were considered nonevaluable for use in cohort analyses, whether PML-RARα NQ− or NQ+, although the calculated PML-RARα NQs for positive samples are included in this chart. Reciprocal GAPDH values: bone marrow, closed circles; peripheral blood, open triangles. The presence of these symbols indicates that the sample was assayed; if the corresponding PML-RARα NQ column is absent and marked with an asterisk, it means that the sample was NQ−. Several bone marrow and peripheral blood samples for patient 2 were assayed by a high-sensitivity (hs) mrtPCR assay,17 as well as by real-time qrtPCR, and ± results are shown below the graph. NT, not tested.
