Molecular detection of clonally rearranged cells in peripheral blood progenitor cell harvests from multiple myeloma patients

Bird, Jennifer M.; Bloxham, D. M.; Samson, Diana; Marcus, Robert; Russell, Nigel H.; Kelsey, Stephen M.; Newland, A. C.; Apperley, JF

doi:10.1111/j.1365-2141.1994.tb04985.x

Cited by 48 publications

(25 citation statements)

References 23 publications

(11 reference statements)

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“…Despite the low level of circulating cells, it is probable that they are responsible for the widespread distribution of malignant cells. The myeloma clone is also detectable in peripheral blood stem cell harvests (Bird et al, 1994;Owen et al, 1996a;Henry et al, 1996), and these cells can be partially or wholly responsible for relapse post-transplant, as has been demonstrated in other diseases (Rill et al, 1994).…”

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Circulating plasma cells in multiple myeloma: characterization and correlation with disease stage

et al. 1997

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Summary. The aim of this study was to develop a flow cytometric test to quantitate low levels of circulating myeloma plasma cells, and to determine the relationship of these cells with disease stage. Cells were characterized using five-parameter flow cytometric analysis with a panel of antibodies, and results were evaluated by comparison with fluorescent consensus-primer IgH-PCR.Bone marrow myeloma plasma cells, defined by high CD38 and Syndecan-1 expression, did not express CD10, 23, 30, 34 or 45RO, and demonstrated weak expression of CD37 and CD45. 65% of patients had CD19 ¹ 56 þ plasma cells, 30% CD19 ¹ 56 low , and 5% CD19 þ 56 þ , and these two antigens discriminated myeloma from normal plasma cells, which were all CD19 þ 56 low .Peripheral blood myeloma plasma cells had the same composite phenotype, but expressed significantly lower levels of CD56 and Syndecan-1, and were detected in 75% (38/51) of patients at presentation, 92% (11/12) of patients in relapse, and 40% (4/10) of stem cell harvests. Circulating plasma cells were not detectable in patients in CR (n ¼ 9) or normals (n ¼ 10), at a sensitivity of up to 1 in 10 000 cells. There was good correlation between the flow cytometric test and IgH-PCR results: myeloma plasma cells were detectable by flow cytometry in all PCR positive samples, and samples with no detectable myeloma plasma cells were PCR negative. Absolute numbers decreased in patients responding to treatment, remained elevated in patients with refractory disease, and increased in patients undergoing relapse. We conclude that flow cytometry can provide an effective aternative to IgH-PCR that will allow quantitative assessment of low levels of residual disease.

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confidence: 99%

Circulating plasma cells in multiple myeloma: characterization and correlation with disease stage

et al. 1997

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“…4 However, these transplants are proved to be contaminated by clonal cells that may contribute to relapse. [5][6][7] A way to reduce the risk of tumor cell contamination in the peripheral blood harvests is through positive CD34 ϩ progenitors selection. Indeed, positive selection of CD34 ϩ cells reduces the contamination of myeloma cells from the apheresis products up to 2 to 4 logs and provides a progenitor cell suspension capable of restoring normal hematopoiesis.…”

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confidence: 99%

Lack of benefit of CD34+ cell selected over non-selected peripheral blood stem cell transplantation in multiple myeloma: results of a single center study

Morineau

Moreau

et al. 2000

Leukemia

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In order to determine the clinical impact of CD34؉ cell selected autologous transplantation in multiple myeloma (MM), we have performed a retrospective case-controlled analysis comparing 21 MM patients receiving high-dose melphalan and autologous transplantation with CD34؉ peripheral blood stem cells (PBSC) as front-line therapy to 21 control patients receiving unselected products. Case matching was performed using the following criteria: age and ␤2-microglobulin at diagnosis and disease status at the time of transplantation. Both cohorts were homogeneous in term of induction treatment and conditioning regimen. Patients were collected for CD34؉ selection after priming with G-CSF alone. Significantly fewer CD34؉ cells/kg were infused to patients in the selected group as compared to patients in the control group: 2.2 (range 0.5-14.3) vs 9.4 (range 1.1-15) (P Ͻ 0.001). The median time to neutrophil recovery у0.05 ؋ 10 9 /l was 10 days for the CD34 ؉ group and 9.5 days for the control group (P ‫؍‬ 0.357). The median time to platelet recovery у 20 ؋ 10 9 /l was 9 days for the CD34 ؉ group and 4.5 days for the control group (P ‫؍‬ 0.005). Response rates were comparable in both groups (85.7% in the CD34 ؉ group vs 90.4% in the control group). At 3 years, event-free survival (32% in the CD34 ؉ group vs 39% in the control group) and overall survival (85% in the CD34 ؉ group vs 79% in the control group) were not significantly different. Finally, use of unselected products dramatically reduced the cost of the transplantation procedure. This study shows that CD34؉ cell selected autologous transplantation is more expensive than transplantation with unselected products and does not improve the clinical outcome of patients with MM. Leukemia (2000) 14, 1815-1820.

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“…3 Patients whose stem cell collections contain plasma cells have a shorter duration of response. 4 Attempts to decrease the number of harvested myeloma cells include in vitro purging with cytotoxic agents, 5 monoclonal antibody purging, 6 and positive selection of CD34-positive cells.…”

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Early harvest and late transplantation as an effective therapeutic strategy in multiple myeloma

Gertz

Lacy

Inwards

et al. 1999

Bone Marrow Transplant

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Summary:Transplantation after high-dose chemotherapy prolongs survival in patients with multiple myeloma compared with standard therapy. It is unclear whether the optimal timing of transplantation is immediately after induction chemotherapy or whether stem cells may be cryopreserved for transplantation at subsequent progression or relapse. In this study, stem cells were collected within 6 months of diagnosis, followed by transplantation only at progression of myeloma. One hundred and eighteen patients with multiple myeloma had stem cells collected and cryopreserved. Eleven had transplants early in the disease after they demonstrated failure to respond to primary therapy. The remaining 107 were eligible for transplants when there was evidence of progressive disease. Of the 118 patients, 67 had transplants, nine died of progressive disease before transplantation, and 42 remain alive in plateau phase. The median survival of the group is 58.5 months; 67 are alive. Serum ␤ 2 -microglobulin, bone marrow labeling index (S phase), and hemoglobin level predicted overall survival (P Ͻ 0.006, P Ͻ 0.001, and P Ͻ 0.01, respectively). We conclude that early cryopreservation of blood stem cells followed by transplantation at progression is a feasible approach to therapy in patients with myeloma. The underlying biology of the disease has a greater impact on survival than the timing of transplantation. A prospective randomized trial is required to answer definitively the question of the optimal timing of blood cell transplantation. Keywords: multiple myeloma; blood cell transplantation; stem cell; myeloma prognosis Multiple myeloma is a malignancy in which chemotherapy dose escalation is an effective strategy capable of high kill of tumor cells, including drug-resistant cells.1 Survival of patients who receive dose-intensive chemotherapy and total body irradiation followed by marrow transplantation is significantly better than for those treated conventionally (60ϩ months and 37 months).2 Peripheral blood stem cell har-

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Molecular detection of clonally rearranged cells in peripheral blood progenitor cell harvests from multiple myeloma patients

Cited by 48 publications

References 23 publications

Circulating plasma cells in multiple myeloma: characterization and correlation with disease stage

Circulating plasma cells in multiple myeloma: characterization and correlation with disease stage

Lack of benefit of CD34+ cell selected over non-selected peripheral blood stem cell transplantation in multiple myeloma: results of a single center study

Early harvest and late transplantation as an effective therapeutic strategy in multiple myeloma

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