Immune Signatures Associated With Clonal Isotype Switch After Autologous Stem Cell Transplantation for Multiple Myeloma
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Immune Signatures Associated With Clonal Isotype Switch After Autologous Stem Cell Transplantation for Multiple Myeloma. / Ye, Rebecca; Kundrapu, Sirisha; Gerson, Stanton L; Driscoll, James J; Beck, Rose; Ali, Naveed; Landgren, Ola; VanHeeckeren, Willem; Luo, George; Kroger, Nicolaus; Caimi, Paolo; De Lima, Marcos; Malek, Ehsan.
In: CL LYMPH MYELOM LEUK, Vol. 19, No. 5, 05.2019, p. e213-e220.Research output: SCORING: Contribution to journal › SCORING: Journal article › Research › peer-review
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TY - JOUR
T1 - Immune Signatures Associated With Clonal Isotype Switch After Autologous Stem Cell Transplantation for Multiple Myeloma
AU - Ye, Rebecca
AU - Kundrapu, Sirisha
AU - Gerson, Stanton L
AU - Driscoll, James J
AU - Beck, Rose
AU - Ali, Naveed
AU - Landgren, Ola
AU - VanHeeckeren, Willem
AU - Luo, George
AU - Kroger, Nicolaus
AU - Caimi, Paolo
AU - De Lima, Marcos
AU - Malek, Ehsan
N1 - Copyright © 2019 Elsevier Inc. All rights reserved.
PY - 2019/5
Y1 - 2019/5
N2 - BACKGROUND: High-dose chemotherapy and autologous stem cell transplantation (ASCT) are integral components of the overall treatment for patients with multiple myeloma (MM) aged ≤ 65 years. The emergence of oligoclonal immunoglobulin bands (ie, immunoglobulins differing from those originally identified at diagnosis [termed clonal isotype switch (CIS)]) has been reported in patients with MM after high-dose chemotherapy followed by autologous stem cell transplantation. However, the clinical relevance and the correlation with immune reconstitution remains unclear.PATIENTS AND METHODS: Patients with MM who had undergone ASCT from 2007 to 2016 were included in the present study. The percentage of natural killer cells, B-cells, and T-cells was measured using flow cytometry in pre- and post-ASCT bone marrow samples. CIS was defined as the appearance of a new serum monoclonal spike on serum protein electrophoresis and immunofixation that differed from original heavy or light chain detected at diagnosis.RESULTS: A retrospective analysis of 177 patients with MM who had undergone ASCT detected CIS in 39 (22%). CIS after ASCT correlated with improved progression-free survival (52.2 vs. 36.6 months; P = .21) and overall survival (75.1 vs. 65.4 months; P = .021). Patients with a relapse had an isotype that differed from a CIS, confirming the benign nature of this phenomenon. CIS was also associated with lower CD8 T-cell percentages and a greater CD4/CD8 ratio (2.8 vs. 0.2; P = .001) compared with patients who did not demonstrate a CIS, suggestive of more profound T-cell immune reconstitution in this group.CONCLUSION: Taken together, our data have demonstrated that a CIS is a benign phenomenon and correlates with a reduced disease burden and enriched immune repertoire beyond the B-cell compartment.
AB - BACKGROUND: High-dose chemotherapy and autologous stem cell transplantation (ASCT) are integral components of the overall treatment for patients with multiple myeloma (MM) aged ≤ 65 years. The emergence of oligoclonal immunoglobulin bands (ie, immunoglobulins differing from those originally identified at diagnosis [termed clonal isotype switch (CIS)]) has been reported in patients with MM after high-dose chemotherapy followed by autologous stem cell transplantation. However, the clinical relevance and the correlation with immune reconstitution remains unclear.PATIENTS AND METHODS: Patients with MM who had undergone ASCT from 2007 to 2016 were included in the present study. The percentage of natural killer cells, B-cells, and T-cells was measured using flow cytometry in pre- and post-ASCT bone marrow samples. CIS was defined as the appearance of a new serum monoclonal spike on serum protein electrophoresis and immunofixation that differed from original heavy or light chain detected at diagnosis.RESULTS: A retrospective analysis of 177 patients with MM who had undergone ASCT detected CIS in 39 (22%). CIS after ASCT correlated with improved progression-free survival (52.2 vs. 36.6 months; P = .21) and overall survival (75.1 vs. 65.4 months; P = .021). Patients with a relapse had an isotype that differed from a CIS, confirming the benign nature of this phenomenon. CIS was also associated with lower CD8 T-cell percentages and a greater CD4/CD8 ratio (2.8 vs. 0.2; P = .001) compared with patients who did not demonstrate a CIS, suggestive of more profound T-cell immune reconstitution in this group.CONCLUSION: Taken together, our data have demonstrated that a CIS is a benign phenomenon and correlates with a reduced disease burden and enriched immune repertoire beyond the B-cell compartment.
U2 - 10.1016/j.clml.2018.12.022
DO - 10.1016/j.clml.2018.12.022
M3 - SCORING: Journal article
C2 - 30878316
VL - 19
SP - e213-e220
JO - CL LYMPH MYELOM LEUK
JF - CL LYMPH MYELOM LEUK
SN - 2152-2650
IS - 5
ER -