CS-PCR fragment analysis in paired MM time point samples
Patient no.*/ Sample† . | Isotype . | Time between samples, y . | Transplantation status‡ . | Treatment response§ . | CS-PCR product . | VDJ-PCR# . | cIgM** . | |
---|---|---|---|---|---|---|---|---|
Length‖ . | PCR type¶ . | |||||||
Patient 1 | ||||||||
BM1 | IgG | 4.2 | ASCT | VGPR | 5389 | B | + | + |
BM2 | IgG | 5389 | B | + | + | |||
Patient 2 | ||||||||
BM1 | IgG | 1.6 | nt | PR | 7114 | B | + | + |
BM2R | IgG | 7114 | B | + | + | |||
Patient 3 | ||||||||
BM1 | IgG | 2.3 | ASCT | SD | 5296 | B | + | − |
BM3R | IgG | 5296 | B | + | − | |||
Patient 4 | ||||||||
BM1 | IgG | 1.6 | ASCT | VGPR | 5914 | B | + | + |
BL2 | IgG | 5914 | B | + | + | |||
Patient 5 | ||||||||
BL1 | IgG | 2.3 | nt | PR | 4565 | B | + | + |
BM2R | IgG | 4565 | B | + | + | |||
Patient 6 | ||||||||
BM1 | IgG | 1.8 | ASCT | PR | 6442 | B | + | − |
BM2R | IgG | 6442 | B | + | + | |||
Patient 7 | ||||||||
BL1 | IgG | 2.8 | ASCT | VGPR | 6500 | AB | + | nd |
BL2R | IgG | 6500 | AB | + | nd | |||
Patient 8 | ||||||||
BM1 | IgA | 1.4 | nt | SD | 5500 | B | + | nd |
BM2 | IgA | 5500 | B | + | nd | |||
Patient 9 | ||||||||
BM1 | IgG | 6.4 | nt | PR | 6000 | AB | + | − |
BL2 | IgG | 6000 | AB | + | + | |||
Patient 10 | ||||||||
BL1 | IgG | 1.8 | nt | PR | 6000 | A | + | + |
BL2 | IgG | 6000 | A | + | + | |||
Patient 11 | ||||||||
BM1 | IgG | 1.7 | nt | SD | 5000 | A | + | nd |
BM2 | IgG | 5000 | A | + | nd | |||
Patient 12 | ||||||||
BM1 | IgG | 1.9 | ALLO | VGPR | 5000 | B | + | nd |
BM2 | IgG | 5000 | B | + | nd | |||
Patient 13 | ||||||||
BL1 | IgA | 2.1 | ASCT | VGPR | 6500 | B | + | − |
BL2 | IgA | 6500 | B | + | − | |||
Patient 14 | ||||||||
BM1R | IgG | 4.7 | ASCT | VGPR | 7500 | A | + | nd |
BM2 | IgG | 7500 | A | + | nd | |||
Patient 15 | ||||||||
BM1 | IgG | 4.8 | ASCT | CR | 8000 | A | + | nd |
BM2 | IgG | 8000 | A | + | nd | |||
Patient 16 | ||||||||
BM1 | IgG | 1.2 | nt | PR | 6000 | B | + | nd |
BM2 | IgG | 6000 | B | + | nd | |||
Patient 17 | ||||||||
BM1 | IgG | 2.3 | nt | PD | 4500 | B | + | nd |
BM2 | IgG | 4500 | B | + | nd | |||
Patient 18 | ||||||||
BL1 | IgG | 6.6 | nt | PR | 3500 | A | + | + |
BL2 | IgG | 3500 | A | + | + | |||
Patient 19 | ||||||||
BM1 | IgG | 1.4 | ASCT | PR | 7000 | A | + | + |
BM2R | IgG | 7000 | A | + | + | |||
Patient 20 | ||||||||
BM1 | IgG | 1.4 | nt | PR | 6000 | B | + | + |
BM2 | IgG | 6000 | B | + | + | |||
Patient 21 | ||||||||
BL1 | IgA | 1.3 | ASCT | VGPR | 8000 | A | + | + |
BL2 | IgA | 8000 | A | + | + | |||
Patient 22 | ||||||||
BM1 | IgA | 1.9 | ASCT | PR | 5000 | B | + | nd |
BM2R | IgA | 5000 | B | + | nd | |||
Patient 23 | ||||||||
BL1 | IgG | 7.6 | ASCT | VGPR | 4500 | B | + | + |
BL2 | IgG | 4500 | B | + | + | |||
Patient 24 | ||||||||
BM1 | IgG | 5.0 | nt | PR | 5000 | B | + | + |
BM2R | IgG | 5000 | B | + | + | |||
Patient 25 | ||||||||
BL1 | IgG | 1.5 | ASCT | PR | 5000 | A | + | nd |
BL2 | IgG | 5000 | A | + | nd | |||
Patient 26 | ||||||||
BM1 | IgG | 2.4 | nt | VGPR | 6000 | B | + | nd |
BM2 | IgG | 6000 | B | + | nd | |||
Patient 27 | ||||||||
BL1 | IgG | 2.0 | nt | PR | 5000 | B | + | + |
BL2 | IgG | 5000 | B | + | + | |||
Patient 28 | ||||||||
BM1 | IgG | 5.0 | ASCT | VGPR | 5500 | AB | + | + |
BL2 | IgG | 5500 | AB | + | + | |||
Patient 29 | ||||||||
BL1 | IgA | 1.9 | ASCT | PR | 3500 | A | + | + |
BL2 | IgA | 3500 | A | + | − | |||
Patient 30 | ||||||||
BM1 | IgG | 1.0 | nt | SD | 6000 | A | + | nd |
BM2 | IgG | 5000 | AB | + | nd | |||
Patient 31 | ||||||||
BM1 | IgA | 7.5 | ASCT | VGPR | 5500 | A | + | + |
BL2 | IgA | 5500 | A | + | + | |||
Patient 32 | ||||||||
BL1 | IgA | 2.9 | ASCT | VGPR | 5000 | A | + | − |
BL2 | IgA | 5000 | A | + | − | |||
Patient 33 | ||||||||
BM1 | IgG | 1.0 | ASCT | VGPR | 5500 | A | + | nd |
BL2 | IgG | - | AB | + | nd | |||
Patient 34 | ||||||||
BM1 | IgA | 6.7 | nt | PR | 5900 | A | + | + |
BL2 | IgA | - | AB | + | + | |||
Patient 35 | ||||||||
BM1 | IgG | 1.0 | ASCT | PR | 6500 | A | + | nd |
BM2 | IgG | - | AB | - | nd | |||
Patient 36 | ||||||||
BL1 | IgG | 4.4 | ASCT | VGPR | 4500 | A | + | − |
BL2 | IgG | - | AB | − | − | |||
Patient 37 | ||||||||
BM1 | IgG | 3.2 | ASCT | PR | 6000 | A | + | nd |
BM2 | IgG | - | AB | − | nd | |||
Patient 38 | ||||||||
BM1 | IgG | 2.0 | ASCT | PR | 9000 | A | + | nd |
BL2 | IgG | − | AB | − | nd | |||
Patient 39 | ||||||||
BM1 | IgG | 1.5 | ASCT | VGPR | − | AB | + | nd |
BM2 | IgG | − | AB | + | nd | |||
Patient 40 | ||||||||
BM1 | IgA | 1.9 | ASCT | PR | − | AB | + | nd |
BM2 | IgA | − | AB | + | nd | |||
Patient 41 | ||||||||
BM1 | IgG | 1.0 | nt | PR | − | AB | − | nd |
BM2 | IgG | − | AB | + | nd |
Patient no.*/ Sample† . | Isotype . | Time between samples, y . | Transplantation status‡ . | Treatment response§ . | CS-PCR product . | VDJ-PCR# . | cIgM** . | |
---|---|---|---|---|---|---|---|---|
Length‖ . | PCR type¶ . | |||||||
Patient 1 | ||||||||
BM1 | IgG | 4.2 | ASCT | VGPR | 5389 | B | + | + |
BM2 | IgG | 5389 | B | + | + | |||
Patient 2 | ||||||||
BM1 | IgG | 1.6 | nt | PR | 7114 | B | + | + |
BM2R | IgG | 7114 | B | + | + | |||
Patient 3 | ||||||||
BM1 | IgG | 2.3 | ASCT | SD | 5296 | B | + | − |
BM3R | IgG | 5296 | B | + | − | |||
Patient 4 | ||||||||
BM1 | IgG | 1.6 | ASCT | VGPR | 5914 | B | + | + |
BL2 | IgG | 5914 | B | + | + | |||
Patient 5 | ||||||||
BL1 | IgG | 2.3 | nt | PR | 4565 | B | + | + |
BM2R | IgG | 4565 | B | + | + | |||
Patient 6 | ||||||||
BM1 | IgG | 1.8 | ASCT | PR | 6442 | B | + | − |
BM2R | IgG | 6442 | B | + | + | |||
Patient 7 | ||||||||
BL1 | IgG | 2.8 | ASCT | VGPR | 6500 | AB | + | nd |
BL2R | IgG | 6500 | AB | + | nd | |||
Patient 8 | ||||||||
BM1 | IgA | 1.4 | nt | SD | 5500 | B | + | nd |
BM2 | IgA | 5500 | B | + | nd | |||
Patient 9 | ||||||||
BM1 | IgG | 6.4 | nt | PR | 6000 | AB | + | − |
BL2 | IgG | 6000 | AB | + | + | |||
Patient 10 | ||||||||
BL1 | IgG | 1.8 | nt | PR | 6000 | A | + | + |
BL2 | IgG | 6000 | A | + | + | |||
Patient 11 | ||||||||
BM1 | IgG | 1.7 | nt | SD | 5000 | A | + | nd |
BM2 | IgG | 5000 | A | + | nd | |||
Patient 12 | ||||||||
BM1 | IgG | 1.9 | ALLO | VGPR | 5000 | B | + | nd |
BM2 | IgG | 5000 | B | + | nd | |||
Patient 13 | ||||||||
BL1 | IgA | 2.1 | ASCT | VGPR | 6500 | B | + | − |
BL2 | IgA | 6500 | B | + | − | |||
Patient 14 | ||||||||
BM1R | IgG | 4.7 | ASCT | VGPR | 7500 | A | + | nd |
BM2 | IgG | 7500 | A | + | nd | |||
Patient 15 | ||||||||
BM1 | IgG | 4.8 | ASCT | CR | 8000 | A | + | nd |
BM2 | IgG | 8000 | A | + | nd | |||
Patient 16 | ||||||||
BM1 | IgG | 1.2 | nt | PR | 6000 | B | + | nd |
BM2 | IgG | 6000 | B | + | nd | |||
Patient 17 | ||||||||
BM1 | IgG | 2.3 | nt | PD | 4500 | B | + | nd |
BM2 | IgG | 4500 | B | + | nd | |||
Patient 18 | ||||||||
BL1 | IgG | 6.6 | nt | PR | 3500 | A | + | + |
BL2 | IgG | 3500 | A | + | + | |||
Patient 19 | ||||||||
BM1 | IgG | 1.4 | ASCT | PR | 7000 | A | + | + |
BM2R | IgG | 7000 | A | + | + | |||
Patient 20 | ||||||||
BM1 | IgG | 1.4 | nt | PR | 6000 | B | + | + |
BM2 | IgG | 6000 | B | + | + | |||
Patient 21 | ||||||||
BL1 | IgA | 1.3 | ASCT | VGPR | 8000 | A | + | + |
BL2 | IgA | 8000 | A | + | + | |||
Patient 22 | ||||||||
BM1 | IgA | 1.9 | ASCT | PR | 5000 | B | + | nd |
BM2R | IgA | 5000 | B | + | nd | |||
Patient 23 | ||||||||
BL1 | IgG | 7.6 | ASCT | VGPR | 4500 | B | + | + |
BL2 | IgG | 4500 | B | + | + | |||
Patient 24 | ||||||||
BM1 | IgG | 5.0 | nt | PR | 5000 | B | + | + |
BM2R | IgG | 5000 | B | + | + | |||
Patient 25 | ||||||||
BL1 | IgG | 1.5 | ASCT | PR | 5000 | A | + | nd |
BL2 | IgG | 5000 | A | + | nd | |||
Patient 26 | ||||||||
BM1 | IgG | 2.4 | nt | VGPR | 6000 | B | + | nd |
BM2 | IgG | 6000 | B | + | nd | |||
Patient 27 | ||||||||
BL1 | IgG | 2.0 | nt | PR | 5000 | B | + | + |
BL2 | IgG | 5000 | B | + | + | |||
Patient 28 | ||||||||
BM1 | IgG | 5.0 | ASCT | VGPR | 5500 | AB | + | + |
BL2 | IgG | 5500 | AB | + | + | |||
Patient 29 | ||||||||
BL1 | IgA | 1.9 | ASCT | PR | 3500 | A | + | + |
BL2 | IgA | 3500 | A | + | − | |||
Patient 30 | ||||||||
BM1 | IgG | 1.0 | nt | SD | 6000 | A | + | nd |
BM2 | IgG | 5000 | AB | + | nd | |||
Patient 31 | ||||||||
BM1 | IgA | 7.5 | ASCT | VGPR | 5500 | A | + | + |
BL2 | IgA | 5500 | A | + | + | |||
Patient 32 | ||||||||
BL1 | IgA | 2.9 | ASCT | VGPR | 5000 | A | + | − |
BL2 | IgA | 5000 | A | + | − | |||
Patient 33 | ||||||||
BM1 | IgG | 1.0 | ASCT | VGPR | 5500 | A | + | nd |
BL2 | IgG | - | AB | + | nd | |||
Patient 34 | ||||||||
BM1 | IgA | 6.7 | nt | PR | 5900 | A | + | + |
BL2 | IgA | - | AB | + | + | |||
Patient 35 | ||||||||
BM1 | IgG | 1.0 | ASCT | PR | 6500 | A | + | nd |
BM2 | IgG | - | AB | - | nd | |||
Patient 36 | ||||||||
BL1 | IgG | 4.4 | ASCT | VGPR | 4500 | A | + | − |
BL2 | IgG | - | AB | − | − | |||
Patient 37 | ||||||||
BM1 | IgG | 3.2 | ASCT | PR | 6000 | A | + | nd |
BM2 | IgG | - | AB | − | nd | |||
Patient 38 | ||||||||
BM1 | IgG | 2.0 | ASCT | PR | 9000 | A | + | nd |
BL2 | IgG | − | AB | − | nd | |||
Patient 39 | ||||||||
BM1 | IgG | 1.5 | ASCT | VGPR | − | AB | + | nd |
BM2 | IgG | − | AB | + | nd | |||
Patient 40 | ||||||||
BM1 | IgA | 1.9 | ASCT | PR | − | AB | + | nd |
BM2 | IgA | − | AB | + | nd | |||
Patient 41 | ||||||||
BM1 | IgG | 1.0 | nt | PR | − | AB | − | nd |
BM2 | IgG | − | AB | + | nd |
Patients 7, 12, 13, 16, 20, and 22 were diagnosed as MM stage II and progressed to MMIII by the second sample. In patient 17, BM1 was diagnosed as MGUS; BM2, as MM1. The remaining patients were MMIII.
Sample codes: BM indicates bone marrow; BL, blood; and R, relapse; numbers designate sample order.
Transplantation status during study interval: ASCT indicates autologous stem cell transplantation; ALLO, allogeneic stem cell transplantation; and nt, did not undergo transplantation.
Response to at least one of the treatments administered during the study interval was as follows: complete response, CR (myeloma clone is clinically undetectable) = 2.4%; very good partial response, VGPR (≥90% decrease in M-component) = 36.6%; partial response, PR (≥50% decrease in M-component) = 48.8%; progressive disease, PD (≥25% increase in M-component) = 2.4%; and stable disease, SD (not satisfying previously mentioned criteria) = 9.8%.
CS-PCR fragment lengths are given in base pairs; for the first 6 patients, switch junctions were identified by sequencing, enabling a more exact determination of the fragment length.
CS-PCR type A and B are single-stage reactions; AB is a nested PCR using A primers in the first stage and B primers in the second stage (Figure 1); + indicates a PCR product was detected; −, no product detected.
V/D/J-PCR indicates presence of MM tumor cells.
cIgM-PCR indicates presence of MM cells expressing clonotypic IgM; nd indicates not tested.