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1. Persistence and Efficacy of Second Generation CAR T Cell Against the LeY Antigen in Acute Myeloid Leukemia

Author

Ritchie, David S., Neeson, Paul J., Khot, Amit, Peinert, Stefan, Tai, Tsin, Tainton, Kellie, Chen, Karen, Shin, Mandy, Wall, Dominic M., Hönemann, Dirk, Gambell, Peter, Westerman, David A., Haurat, Javier, Westwood, Jennifer A., Scott, Andrew M., Kravets, Lucy, Dickinson, Michael, Trapani, Joseph A., Smyth, Mark J., Darcy, Phillip K., Kershaw, Michael H., and Prince, H. Miles

Published
2013
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8. Accurate white blood cell differential by Alinity hq: A comparison with flow cytometry and manual differential.

Author

Gambell, Peter, Rowley, Grant, Pham, Tracy Anh Thu, Dang, Theresa Loan, Mulumba, Huguette, Smith, Larry, and Lakos, Gabriella

Subjects
*CELL differentiation, *FLOW cytometry, *LEUCOCYTES, *HEMATOLOGY, *AUTOANALYZERS, *COMPARATIVE studies
Abstract

Introduction: White blood cell (WBC) differential by flow cytometry can report a six‐part WBC differential and enumerate blasts. Some modern hematology analyzers are also able to provide a six‐part WBC differential (including immature granulocytes). Our goal was to compare the WBC differential obtained by the Abbott Alinity hq hematology analyzer to an 8‐color single‐tube flow cytometry method and to manual WBC differential. Methods: Samples from 144 patients were tested with Alinity hq, flow cytometry, and microscopic WBC differential. The WBC count ranged from 1.22 to 359 × 109/L, and 34 samples were flagged by the analyzer for abnormal WBC morphology. Results: Strong concordance was demonstrated between Alinity hq and flow cytometry for all six components of the differential, with correlation coefficients ranging from 0.86 (basophils) to 1.00 (lymphocytes). Small, clinically insignificant positive difference was observed between Alinity hq and flow cytometry for mature and total neutrophils (2.51% and 1.85%) and eosinophils (0.14%), and small negative difference for immature granulocytes (−0.65%), lymphocytes (−0.61%), and basophils (−0.21%). No bias was detected between the Alinity hq and flow cytometry monocyte counts. Alinity hq and flow cytometry results agreed with the manual differential, apart from small, clinically insignificant differences. Alinity hq nucleated red blood cell concentrations were equivalent with the manual results (r = 0.95, slope = 1.16). The percentage of blasts by flow cytometry demonstrated good correlation and agreement with the manual count (r = 0.99, slope = 1.35). Conclusion: Alinity hq has produced accurate six‐part WBC differential in this three‐way comparison, equivalent to flow cytometry and morphological classification. [ABSTRACT FROM AUTHOR]

Published
2022
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9. Negative selection of chronic lymphocytic leukaemia cells using a bifunctional rosette-based antibody cocktail

Author

Westerman David, Carney Dennis, Essakali Salim, Gambell Peter, Seymour John F, and Dobrovic Alexander

Subjects
Biotechnology, TP248.13-248.65
Abstract

Abstract Background High purity of tumour samples is a necessity for accurate genetic and expression analysis and is usually achieved by positive selection in chronic lymphocytic leukaemia (CLL). Results We adapted a bifunctional rosette-based antibody cocktail for negative selection of B-cells for isolating CLL cells from peripheral blood (PB). PB samples from CLL patients were split into aliquots. One aliquot of each sample was enriched by density gradient centrifugation (DGC), while the other aliquot of each sample was incubated with an antibody cocktail for B-cell enrichment prior to DGC (RS+DGC). The purity of CLL cells after DGC averaged 74.1% (range: 15.9 – 97.4%). Using RS+DGC, the purity averaged 93.8% (range: 80.4 – 99.4%) with 23 of 29 (79%) samples showing CLL purities above 90%. RNA extracted from enriched CLL cells was of appropriately high quality for microarray analysis. Conclusion This study confirms the use of a bifunctional rosette-based antibody cocktail as an effective method for the purification of CLL cells from peripheral blood.

Published
2008
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10. Reproducible diagnosis of chronic lymphocytic leukemia by flow cytometry : An European Research Initiative on CLL (ERIC) & European Society for Clinical Cell Analysis (ESCCA) Harmonisation project

Author

Rawstron, Andy C., Kreuzer, Karl-Anton, Soosapilla, Asha, Spacek, Martin, Stehlikova, Olga, Gambell, Peter, McIver-Brown, Neil, Villamor, Neus, Psarra, Katherina, Arroz, Maria, Milani, Raffaella, de la Serna, Javier, Teresa Cedena, M., Jaksic, Ozren, Nomdedeu, Josep, Moreno, Carol, Rigolin, Gian Matteo, Cuneo, Antonio, Johansen, Preben, Johnsen, Hans E., Rosenquist, Richard, Niemann, Carsten Utoft, Kern, Wolfgang, Westerman, David, Trneny, Marek, Mulligan, Stephen, Doubek, Michael, Pospisilova, Sarka, Hillmen, Peter, Oscier, David, Hallek, Michael, Ghia, Paolo, Montserrat, Emili, Rawstron, Andy C., Kreuzer, Karl-Anton, Soosapilla, Asha, Spacek, Martin, Stehlikova, Olga, Gambell, Peter, McIver-Brown, Neil, Villamor, Neus, Psarra, Katherina, Arroz, Maria, Milani, Raffaella, de la Serna, Javier, Teresa Cedena, M., Jaksic, Ozren, Nomdedeu, Josep, Moreno, Carol, Rigolin, Gian Matteo, Cuneo, Antonio, Johansen, Preben, Johnsen, Hans E., Rosenquist, Richard, Niemann, Carsten Utoft, Kern, Wolfgang, Westerman, David, Trneny, Marek, Mulligan, Stephen, Doubek, Michael, Pospisilova, Sarka, Hillmen, Peter, Oscier, David, Hallek, Michael, Ghia, Paolo, and Montserrat, Emili

Abstract

The diagnostic criteria for CLL rely on morphology and immunophenotype. Current approaches have limitations affecting reproducibility and there is no consensus on the role of new markers. The aim of this project was to identify reproducible criteria and consensus on markers recommended for the diagnosis of CLL. ERIC/ESCCA members classified 14 of 35 potential markers as “required” or “recommended” for CLL diagnosis, consensus being defined as >75% and >50% agreement, respectively. An approach to validate “required” markers using normal peripheral blood was developed. Responses were received from 150 participants with a diagnostic workload >20 CLL cases per week in 23/150 (15%), 5–20 in 82/150 (55%), and <5 cases per week in 45/150 (30%). The consensus for “required” diagnostic markers included: CD19, CD5, CD20, CD23, Kappa, and Lambda. “Recommended” markers potentially useful for differential diagnosis were: CD43, CD79b, CD81, CD200, CD10, and ROR1. Reproducible criteria for component reagents were assessed retrospectively in 14,643 cases from 13 different centers and showed >97% concordance with current approaches. A pilot study to validate staining quality was completed in 11 centers. Markers considered as “required” for the diagnosis of CLL by the participants in this study (CD19, CD5, CD20, CD23, Kappa, and Lambda) are consistent with current diagnostic criteria and practice. Importantly, a reproducible approach to validate and apply these markers in individual laboratories has been identified. Finally, a consensus “recommended” panel of markers to refine diagnosis in borderline cases (CD43, CD79b, CD81, CD200, CD10, and ROR1) has been defined and will be prospectively evaluated.

Published
2018
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11. Reproducible diagnosis of chronic lymphocytic leukemia by flow cytometry:An European Research Initiative on CLL (ERIC) & European Society for Clinical Cell Analysis (ESCCA) Harmonisation project

Author

Rawstron, Andy C., Kreuzer, Karl-anton, Soosapilla, Asha, Spacek, Martin, Stehlikova, Olga, Gambell, Peter, Mciver-brown, Neil, Villamor, Neus, Psarra, Katherina, Arroz, Maria, Milani, Raffaella, De La Serna, Javier, Cedena, M. Teresa, Jaksic, Ozren, Nomdedeu, Josep, Moreno, Carol, Rigolin, Gian Matteo, Cuneo, Antonio, Johansen, Preben, Johnsen, Hans E., Rosenquist, Richard, Niemann, Carsten Utoft, Kern, Wolfgang, Westerman, David, Trneny, Marek, Mulligan, Stephen, Doubek, Michael, Pospisilova, Sarka, Hillmen, Peter, Oscier, David, Hallek, Michael, Ghia, Paolo, Montserrat, Emili, Rawstron, Andy C., Kreuzer, Karl-anton, Soosapilla, Asha, Spacek, Martin, Stehlikova, Olga, Gambell, Peter, Mciver-brown, Neil, Villamor, Neus, Psarra, Katherina, Arroz, Maria, Milani, Raffaella, De La Serna, Javier, Cedena, M. Teresa, Jaksic, Ozren, Nomdedeu, Josep, Moreno, Carol, Rigolin, Gian Matteo, Cuneo, Antonio, Johansen, Preben, Johnsen, Hans E., Rosenquist, Richard, Niemann, Carsten Utoft, Kern, Wolfgang, Westerman, David, Trneny, Marek, Mulligan, Stephen, Doubek, Michael, Pospisilova, Sarka, Hillmen, Peter, Oscier, David, Hallek, Michael, Ghia, Paolo, and Montserrat, Emili

Published
2018

12. Reproducible diagnosis of chronic lymphocytic leukemia by flow cytometry: An European Research Initiative on CLL (ERIC) & European Society for Clinical Cell Analysis (ESCCA) Harmonisation project

Author

Rawstron, Andy C., primary, Kreuzer, Karl-Anton, additional, Soosapilla, Asha, additional, Spacek, Martin, additional, Stehlikova, Olga, additional, Gambell, Peter, additional, McIver-Brown, Neil, additional, Villamor, Neus, additional, Psarra, Katherina, additional, Arroz, Maria, additional, Milani, Raffaella, additional, de la Serna, Javier, additional, Cedena, M. Teresa, additional, Jaksic, Ozren, additional, Nomdedeu, Josep, additional, Moreno, Carol, additional, Rigolin, Gian Matteo, additional, Cuneo, Antonio, additional, Johansen, Preben, additional, Johnsen, Hans E., additional, Rosenquist, Richard, additional, Niemann, Carsten Utoft, additional, Kern, Wolfgang, additional, Westerman, David, additional, Trneny, Marek, additional, Mulligan, Stephen, additional, Doubek, Michael, additional, Pospisilova, Sarka, additional, Hillmen, Peter, additional, Oscier, David, additional, Hallek, Michael, additional, Ghia, Paolo, additional, and Montserrat, Emili, additional

Published
2018
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13. Reproducible Diagnosis of Chronic Lymphocytic Leukemia (CLL) By Flow Cytometry : An European Research Initiative on CLL (ERIC) & European Society for Clinical Cell Analysis (ESCCA) Harmonisation Project

Author

Rawstron, Andy C., Kreuzer, Karl-Anton, Soosapilla, Asha, Spacek, Martin, Gambell, Peter, McIver-brown, Neil, Psarra, Katherina, Arroz, Maria, Milani, Raffaella, de la Serna, Javier, Teresa Cedena, M., Jaksic, Ozren, Nomdedeu, Josep F., Moreno, Carol, Rigolin, Gian Matteo, Cuneo, Antonio, Johansen, Preben, Johnsen, Hans Erik, Rosenquist, Richard, Niemann, Carsten Utoft, Kern, Wolfgang, Westerman, David A., Trneny, Marek, Mulligan, Stephen P., Hillmen, Peter, Oscier, David G., Hallek, Michael, Ghia, Paolo, Montserrat, Emili, Rawstron, Andy C., Kreuzer, Karl-Anton, Soosapilla, Asha, Spacek, Martin, Gambell, Peter, McIver-brown, Neil, Psarra, Katherina, Arroz, Maria, Milani, Raffaella, de la Serna, Javier, Teresa Cedena, M., Jaksic, Ozren, Nomdedeu, Josep F., Moreno, Carol, Rigolin, Gian Matteo, Cuneo, Antonio, Johansen, Preben, Johnsen, Hans Erik, Rosenquist, Richard, Niemann, Carsten Utoft, Kern, Wolfgang, Westerman, David A., Trneny, Marek, Mulligan, Stephen P., Hillmen, Peter, Oscier, David G., Hallek, Michael, Ghia, Paolo, and Montserrat, Emili

Published
2015

14. Reproducible Diagnosis of Chronic Lymphocytic Leukemia (CLL) By Flow Cytometry: An European Research Initiative on CLL (ERIC) & European Society for Clinical Cell Analysis (ESCCA) Harmonisation Project

Author

Rawstron, Andy C, primary, Kreuzer, Karl-Anton, additional, Soosapilla, Asha, additional, Spacek, Martin, additional, Gambell, Peter, additional, McIver-brown, Neil, additional, Psarra, Katherina, additional, Arroz, Maria, additional, Milani, Raffaella, additional, de la Serna, Javier, additional, Cedena, M. Teresa, additional, Jaksic, Ozren, additional, Nomdedeu, Josep F., additional, Moreno, Carol, additional, Rigolin, Gian Matteo, additional, Cuneo, Antonio, additional, Johansen, Preben, additional, Johnsen, Hans Erik, additional, Rosenquist, Richard, additional, Niemann, Carsten Utoft, additional, Kern, Wolfgang, additional, Westerman, David A, additional, Trneny, Marek, additional, Mulligan, Stephen P., additional, Hillmen, Peter, additional, Oscier, David G, additional, Hallek, Michael, additional, Ghia, Paolo, additional, and Montserrat, Emili, additional

Published
2015
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15. A Complementary Role of High Throughput Sequencing and Multiparameter Cytometry for Minimal Residual Disease (MRD) Detection in Chronic Lymphocytic Leukemia (CLL):an European Research Initiative (ERIC) Study

Author

Rawstron, Andy, Fazi, Claudia, Villamor, Neus, Delgado, Julio, Letestu, Remi, Cymbalista, Florence, Palacio, Carlos, Bosch, Francesc, De Tute, Ruth M., Liptrot, Stuart, O'Brien, David, Spacek, Martin, Dobber, Johan, Kater, Arnon P., Gambell, Peter C., Westerman, David A., Soosapilla, Asha, Mulligan, Stephen P., Lozanski, Gerard, Lin, Ke, Pettitt, Andrew R., Brachtl, Gabi, Egle, Alexander, Williamson, David W., Sanders, Catherine M., Robins, Harlan, Boysen, Justin, Shanafelt, Tait D., Hanson, Curtis A., Jorgensen, Jeffrey L., Wierda, William G., Yuan, Constance, Stetler-Stevenson, Maryalice, Rassenti, Laura, Broome, H. Elizabeth, Kipps, Thomas J., Hauwel, Mathieu, Marinov, Iuri, Craig, Fiona E., Josep, Nomdedeu, Moreno, Carol, Stehlikova, Olga, Doubek, Michael, Pospisilova, Sarka, Kreuzer, Karl-Anton, Hallek, Michael, Hillmen, Peter, Montserrat, Emili, Ghia, Paolo, Rawstron, Andy, Fazi, Claudia, Villamor, Neus, Delgado, Julio, Letestu, Remi, Cymbalista, Florence, Palacio, Carlos, Bosch, Francesc, De Tute, Ruth M., Liptrot, Stuart, O'Brien, David, Spacek, Martin, Dobber, Johan, Kater, Arnon P., Gambell, Peter C., Westerman, David A., Soosapilla, Asha, Mulligan, Stephen P., Lozanski, Gerard, Lin, Ke, Pettitt, Andrew R., Brachtl, Gabi, Egle, Alexander, Williamson, David W., Sanders, Catherine M., Robins, Harlan, Boysen, Justin, Shanafelt, Tait D., Hanson, Curtis A., Jorgensen, Jeffrey L., Wierda, William G., Yuan, Constance, Stetler-Stevenson, Maryalice, Rassenti, Laura, Broome, H. Elizabeth, Kipps, Thomas J., Hauwel, Mathieu, Marinov, Iuri, Craig, Fiona E., Josep, Nomdedeu, Moreno, Carol, Stehlikova, Olga, Doubek, Michael, Pospisilova, Sarka, Kreuzer, Karl-Anton, Hallek, Michael, Hillmen, Peter, Montserrat, Emili, and Ghia, Paolo

Published
2014

16. A Complementary Role of High Throughput Sequencing and Multiparameter Cytometry for Minimal Residual Disease (MRD) Detection in Chronic Lymphocytic Leukemia (CLL):an European Research Initiative (ERIC) Study

Author

Rawstron, Andy, primary, Fazi, Claudia, additional, Villamor, Neus, additional, Delgado, Julio, additional, Letestu, Remi, additional, Cymbalista, Florence, additional, Palacio, Carlos, additional, Bosch, Francesc, additional, De Tute, Ruth M, additional, Liptrot, Stuart, additional, O'Brien, David, additional, Spacek, Martin, additional, Dobber, Johan, additional, Kater, Arnon P., additional, Gambell, Peter C, additional, Westerman, David A, additional, Soosapilla, Asha, additional, Mulligan, Stephen P., additional, Lozanski, Gerard, additional, Lin, Ke, additional, Pettitt, Andrew R, additional, Brachtl, Gabi, additional, Egle, Alexander, additional, Williamson, David W, additional, Sanders, Catherine M, additional, Robins, Harlan, additional, Boysen, Justin, additional, Shanafelt, Tait D., additional, Hanson, Curtis A., additional, Jorgensen, Jeffrey L., additional, Wierda, William G., additional, Yuan, Constance, additional, Stetler-Stevenson, Maryalice, additional, Rassenti, Laura, additional, Broome, H. Elizabeth, additional, Kipps, Thomas J., additional, Hauwel, Mathieu, additional, Marinov, Iuri, additional, Craig, Fiona E., additional, Josep, Nomdedeu, additional, Moreno, Carol, additional, Stehlikova, Olga, additional, Doubek, Michael, additional, Pospisilova, Sarka, additional, Kreuzer, Karl-Anton, additional, Hallek, Michael, additional, Hillmen, Peter, additional, Montserrat, Emili, additional, and Ghia, Paolo, additional

Published
2014
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17. In vivo trafficking, persistence and efficacy of Lewis-Y chimeric antigen receptor T cells in patients with Lewis-Y positive acute myeloid leukaemia (P4354)

Author

Neeson, Paul, primary, Ritchie, David, additional, Khot, Amit, additional, Peinert, Stefan, additional, Tai, Tsin, additional, Honemann, Dirk, additional, Gambell, Peter, additional, Westerman, David, additional, Westwood, Jennifer, additional, Scott, Andrew, additional, Kravets, Lucy, additional, Dickinson, Michael, additional, Trapani, Joseph, additional, Smyth, Mark, additional, Darcy, Phillip, additional, Kershaw, Michael, additional, and Prince, H., additional

Published
2013
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23. Targeting Lewis Y-Positive Multiple Myeloma and Acute Myeloid Leukemia with Gene-Modified T Cells Demonstrating Memory Phenotype

Author

Peinert, Stefan, primary, Ritchie, David S., additional, Hoenemann, Dirk, additional, Harrison, Simon J., additional, Guru, Preethi, additional, Kershaw, Michael H., additional, Shin, Amanda, additional, Smyth, Mark J., additional, Trapani, Joseph A., additional, Scott, Andrew M, additional, Cartwright, Glenn A, additional, Smyth, Fiona E, additional, Power, Barbara E, additional, Darcy, Phillip K., additional, Gambell, Peter, additional, Westerman, David, additional, Neeson, Paul, additional, and Prince, H. Miles, additional

Published
2008
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30. Reproducible diagnosis of CLL by flow cytometry: an ERIC & ESCCA harmonisation project

Author

Rawstron, Andy, Kreuzer, Karl-Anton, Soosapilla, Asha, Spacek, Martin, Gambell, Peter, Mciver-Brown, Neil, Psarra, Katherina, Arroz, Maria, Milani, Raffaella, La Serna, Javier, Cedena, M. Teresa, Jaksic, Ozren, Nomdedeu, Josep, Moreno, Carol, Rigolin, Gian Matteo, Cuneo, Antonio, Johansen, Preben, Johnsen, Hans Erik, Rosenquist, Richard, Niemann, Carsten, Westerman, David, Trneny, Marek, Mulligan, Stephen, Hillmen, Peter, Oscier, David, Michael Hallek, Ghia, Paolo, and Montserrat, Emili

Subjects
CLL, flow cytometry, flow cytometry, CLL, NO

31. Reproducible diagnosis of chronic lymphocytic leukemia by flow cytometry:An European Research Initiative on CLL (ERIC) & European Society for Clinical Cell Analysis (ESCCA) Harmonisation project

Author

Rawstron, AC, Kreuzer, K-A, Soosapilla, A, Spacek, M, Stehlikova, O, Gambell, P, McIver-Brown, N, Villamor, N, Psarra, K, Arroz, M, Milani, R, de la Serna, J, Cedena, MT, Jaksic, O, Nomdedeu, J, Moreno, C, Rigolin, GM, Cuneo, A, Johansen, P, Johnsen, HE, Rosenquist, R, Niemann, CU, Kern, W, Westerman, D, Trneny, M, Mulligan, S, Doubek, M, Pospisilova, S, Hillmen, P, Oscier, D, Hallek, M, Ghia, P, Montserrat, E, Rawstron, Andy C., Kreuzer, Karl-Anton, Soosapilla, Asha, Spacek, Martin, Stehlikova, Olga, Gambell, Peter, McIver-Brown, Neil, Villamor, Neu, Psarra, Katherina, Arroz, Maria, Milani, Raffaella, de la Serna, Javier, Cedena, M. Teresa, Jaksic, Ozren, Nomdedeu, Josep, Moreno, Carol, Rigolin, Gian Matteo, Cuneo, Antonio, Johansen, Preben, Johnsen, Hans E., Rosenquist, Richard, Niemann, Carsten Utoft, Kern, Wolfgang, Westerman, David, Trneny, Marek, Mulligan, Stephen, Doubek, Michael, Pospisilova, Sarka, Hillmen, Peter, Oscier, David, Hallek, Michael, Ghia, Paolo, and Montserrat, Emili

Subjects
chronic lymphocytic leukemia, diagnosis, flow cytometry, 2734, Histology, Cell Biology, Clinical Laboratory Medicine, Reproducibility of Results, Pilot Projects, Original Articles, Leukemia, Lymphocytic, Chronic, B-Cell, NO, Immunophenotyping, diagnosi, Klinisk laboratoriemedicin, immune system diseases, hemic and lymphatic diseases, Biomarkers, Tumor, Humans, Original Article, Retrospective Studies
Abstract

The diagnostic criteria for CLL rely on morphology and immunophenotype. Current approaches have limitations affecting reproducibility and there is no consensus on the role of new markers. The aim of this project was to identify reproducible criteria and consensus on markers recommended for the diagnosis of CLL. ERIC/ESCCA members classified 14 of 35 potential markers as “required” or “recommended” for CLL diagnosis, consensus being defined as >75% and >50% agreement, respectively. An approach to validate “required” markers using normal peripheral blood was developed. Responses were received from 150 participants with a diagnostic workload >20 CLL cases per week in 23/150 (15%), 5–20 in 82/150 (55%), and 97% concordance with current approaches. A pilot study to validate staining quality was completed in 11 centers. Markers considered as “required” for the diagnosis of CLL by the participants in this study (CD19, CD5, CD20, CD23, Kappa, and Lambda) are consistent with current diagnostic criteria and practice. Importantly, a reproducible approach to validate and apply these markers in individual laboratories has been identified. Finally, a consensus “recommended” panel of markers to refine diagnosis in borderline cases (CD43, CD79b, CD81, CD200, CD10, and ROR1) has been defined and will be prospectively evaluated. © 2017 International Clinical Cytometry Society.

Published
2018
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32. Patients with multiple myeloma treated with thalidomide: evaluation of clinical parameters, cytokines,angiogenic markers, mast cells and marrow CD57+ cytotoxic T cells as predictors of outcome.

Author

Mileshkin L, Honemann D, Gambell P, Trivett M, Hayakawa Y, Smyth M, Beshay V, Ritchie D, Simmons P, Milner AD, Zeldis JB, and Prince HM

Subjects
Adult, Aged, Clinical Trials, Phase II as Topic statistics & numerical data, Disease-Free Survival, Female, Humans, Kaplan-Meier Estimate, Male, Middle Aged, Multicenter Studies as Topic statistics & numerical data, Multiple Myeloma blood, Multiple Myeloma mortality, Multiple Myeloma pathology, Neoplasm Proteins blood, Neovascularization, Pathologic drug therapy, Neovascularization, Pathologic pathology, Prognosis, Survival Analysis, T-Lymphocytes, Cytotoxic chemistry, Treatment Outcome, Angiogenesis Inhibitors therapeutic use, Antineoplastic Agents therapeutic use, Biomarkers, Tumor blood, Bone Marrow pathology, CD57 Antigens analysis, Cytokines blood, Immunologic Factors therapeutic use, Mast Cells pathology, Multiple Myeloma drug therapy, T-Lymphocytes, Cytotoxic pathology, Thalidomide therapeutic use
Abstract

Background and Objectives: In vitro studies suggest that thalidomide has an immunoregulatory role and alters the marrow microenvironment. We assessed laboratory and clinical parameters in patients with myeloma treated with thalidomide as potential prognostic markers and looked for changes with therapy., Design and Methods: Seventy-five patients with relapsed/refractory myeloma received thalidomide in a phase II trial. Serial samples of platelet-poor plasma and bone marrow were tested for angiogenic cytokines including vascular endothelial growth factor (VEGF), marrow microvessel-density (MVD), mast cells and CD57+ cell expression. The effects of these parameters on response rate (RR), progression-free survival (PFS) and overall survival (OS) were analyzed., Results: Elevated baseline VEGF predicted for a superior RR (p=0.018) and PFS. Elevated CD57+ cells also predicted superior PFS (p=0.012). MVD did not predict for RR, PFS or OS, but MVD and VEGF fell significantly in responders. Multivariate analysis identified that inferior OS was associated with age >65 years (p=0.017), raised lactate dehydrogenase (p=0.001), raised hepatocyte growth factor levels (p=0.012) and low pre-treatment CD57+ cells (p<0.001)., Interpretation and Conclusions: Our findings support the suggestion that thalidomide has anti-angiogenic and immunomodulatory effects in myeloma. The preferred method for assessing angiogenesis is plasma VEGF levels and the assessment of CD57+ cells for patients with myeloma receiving novel immunomodulatory drugs should be further investigated.

Published
2007
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