a normal HLC result was always concordant with electrophoretic CR while an abnormal HLC result was always concordant with electrophoretic non-CR

a normal HLC result was always concordant with electrophoretic CR while an abnormal HLC result was always concordant with electrophoretic non-CR. over conventional electrophoretic response in predicting outcomes done on archived samples of patients enrolled in Blood Marrow Transplant Clinical Trials Network Tonapofylline (BMTCTN) 0102, a randomized phase 3 multicentre trial aimed at determining the role of tandem autologous or allogeneic second transplant after upfront autologous haematopoietic cell transplant (HCT) Tonapofylline in MM (Krishnan, et al 2011). Eligible patients were biologically assigned to receive a tandem allogeneic (alloHCT) or a second autologous (autoHCT) transplant, based on availability of a human leucocyte antigen (HLA)-matched sibling donor. The tandem autoHCT group was re-randomized to receive 1 year of maintenance therapy with thalidomide plus dexamethasone vs. observation. De-identified, archived cryopreserved serum samples collected prior to first transplant, day 56 and 1 year post-second transplant banked at the National Heart Lung and Blood Institute (NHLBI) sample biorepository were used in this study using an Institutional Review Board-approved protocol. Samples were processed at The Binding Site, Birmingham, UK. Tonapofylline Testing was performed using a Siemens BNII nephelometer for free kappa and free lambda (FLC Freelite? kits), IgG and IgG, IgA and IgA, IgM and IgM (HLC IgG, IgA and IgM Hevylite? kits). The normal ranges for ratios of the FLC and HLC assays Rabbit Polyclonal to SERINC2 were determined by analysis of serum samples from 146 normal controls and were: FLC / 0.26C1.65; HLC IgG / 0.98C2.75; HLC IgA / 0.8C2.04 and IgM / 0.96C2.3. Twenty-eight samples could not be analysed due to inadequate sample collection; 1 patient with disease progression at study entry (auto-auto arm) was excluded; 490 samples were analysed. The International Uniform Response Criteria (Durie, et al 2006) was used to define disease response with the addition of near complete response (CR), which was defined as evidence of disease by immunofixation electrophoresis without morphological evidence of MM in bone marrow.(Krishnan, et al 2011) Normalization of HLC ratios across all 3 measured heavy/light chain pairs or normal clonal isotype with normal ratios of uninvolved pairs was considered HLC-R while normalization of the FLC ratio was called FLC remission (FLC-R). The HLC result of any HLC pair missing for a given time was disregarded, thus decreasing the number of interpretable HLC compared to FLC ratios (Table I). Table I Characteristics of study patients and results of HLC and FLC testing thead th valign=”middle” align=”left” rowspan=”1″ colspan=”1″ /th th valign=”middle” align=”center” rowspan=”1″ colspan=”1″ AutoHCT br / N (%) br / (n=331) /th th valign=”middle” align=”center” rowspan=”1″ Tonapofylline colspan=”1″ AlloHCT br / N (%) br / (n=166) /th th valign=”middle” align=”center” rowspan=”1″ colspan=”1″ P- value /th /thead hr / Male207 (63)94 (57)02 hr / Median age, years (range)56 (23C70)51 (29C68) 0001 hr / Race003?African American43 (13)9 (5)?Caucasian246 (74)136 (82)?Other42 (13)21 (13) hr / Karnofsky score 90253 (76)129 (78)06 hr / -2 Microglobulin, median2.12.009 hr / Durie-Salmon03?Stage ICII100 (30)40 (24)?Stage III231 (70)126 (76) hr / 0102 Risk Status*0.01?High34 (10)30 (18)?Standard297 (90)136 (82) hr / Disease Status at Transplant02?CR33 (10)23 (14)?Near CR50 (15)15 (9)?VGPR54 (16)36 (22)?PR125 (38)64 (38)?MR24 (7)13 (8)?SD17 (5)7 (4)?Not Evaluable22 (7)5(3)?Unknown6(2)3(2) hr / Treatment arm in auto-autoC?Thalidomide/Dexamethasone169 (51)C?Observation162 (49)C hr / No second transplant58 (17)31 (19)0.8 hr / Median follow-up of survivors from 1st transplant87 (7C105)81 (15C105)0.7 hr / FLC-R pre-1st transplant, total N=490105 (32)49 (29)0.6 hr / HLC-R pre-1st transplant, total N=4851211(67)111 (64)0.5 Open in a separate window *-High risk defined as beta2 microglobulin 4 mg/dl and deletion 13 by standard karyotype 1HLC results are a composite of all heavy and light chain combinations with normal or low concentration plus any normal heavy chain kappa/lambda ratios if any result is missing it will decrease the.