Immune-mediated neuromuscular complications of graft-versus-host disease.

INTRODUCTION/AIMS: We aimed to describe the clinical phenotype, histopathological findings and overall survival (OS) of the immune-mediated neuromuscular complications of graft-versus-host disease (GVHD). METHODS: We conducted a retrospective chart review of adult patients presenting with immune-mediated neuromuscular complications of GVHD to Mayo Clinic, between April 2013 and July 2018.We collected clinical and laboratory characteristics, histopathological findings, response to treatment and survival data. RESULTS: We identified 20 patients with a mean age at presentation of 55 y. Mean time from transplant to neurological presentation was 14 mo. Myositis was the most common complication seen in 17 patients, manifesting with predominantly axial and/or proximal weakness. Eleven patients had a muscle biopsy showing diffuse perimysial, predominantly macrophagic infiltration in 10, 3 of them with perimysial perivascular lymphocytic collections, and endomysial and perimysial lymphocytic infiltration in 1. Only two patients had a neuropathic complication: one each with acute inflammatory demyelinating polyradiculoneuropathy and neuralgic amyotrophy. A single patient had a myasthenic syndrome presenting with fluctuating foot drop. Nineteen patients were treated and all responded to immunosuppressive agents; however, 11 had further GVHD flares requiring escalation of therapy. After a median follow-up of 83 mo, seven (35%) patients died: five from progressive GVHD and two from infections. The 5-y OS from time of transplant was 68%. DISCUSSION: Myositis is the most common immune-mediated neuromuscular complication of GVHD while peripheral neuropathy and myasthenic syndromes appear less common. The macrophage-predominant infiltration on muscle biopsy deserves further study to better clarify the role of macrophages in GVHD pathogenesis.

Venetoclax for the treatment of multiple myeloma: Outcomes outside of clinical trials.

Multiple myeloma (MM) remains an incurable disease despite incorporation of novel agents. Venetoclax, a B-cell lymphoma 2 (BCL-2) inhibitor is approved for some hematologic malignancies but not yet for MM, although clinical trials have shown efficacy in patients with MM, particularly those harboring t(11;14). We reviewed the medical records of relapsed and/or refractory MM patients to study the efficacy and safety of venetoclax used outside of clinical trials at Mayo Clinic between December, 2016 and March, 2019. The data cut-off date was August 06, 2020. We identified 56 patients of whom 42 (75%) harbored t(11;14). The median number of prior therapies was six (range 1-15) and 14% of patients had received ≥10 prior lines of therapy. Fifty-three (95%) patients were refractory to an immunomodulatory drug and proteasome inhibitor. Venetoclax was used as monotherapy or doublet, in combination with dexamethasone in 55% (n = 31) and a triplet or quadruplet in 45% of patients. No patient experienced tumor lysis syndrome. Overall response rate in 52 evaluable patients was 44%. The median time to best response was 2 months and median duration of response was 13.6 months. The median PFS for the entire cohort was 5.8 (95% CI 4.9-10.3) months and median OS was 28.4 (95% CI 14.6-not reached) months. The presence of t(11;14) was associated with improved PFS (median 9.7 months vs. 4.2 months, p = 0.019) and OS (median not reached vs. 10.8 9 months, p = 0.015). Venetoclax demonstrates encouraging activity in heavily-treated patients with relapsed/refractory MM, particularly the t(11;14) patient-population.

Comparison of the current renal staging, progression and response criteria to predict renal survival in AL amyloidosis using a Mayo cohort.

Three sets of criteria (International Society of Amyloidosis [ISA], Palladini and Kastritis) were independently developed for staging, progression and response criteria to predict renal survival in patients with AL amyloidosis. We evaluated these criteria using a cohort of 495 newly diagnosed AL amyloidosis patients with renal involvement using time to event competing risk analysis at baseline, 3, 6 and 12 months after treatment. Only Palladini and Kastritis had a staging system and both predicted a higher risk of end stage renal disease (ESRD) in the stage III vs stage I patients but only the Palladini model was predictive for stage II patients. At 3 months, risk of ESRD was significantly higher for Palladini and ISA renal progression (hazard ratio [HR] 2.8 [95% CI: 1.5-5.3, p = .001] and 2.5 [CI: 1.4-4.6, p = .004, respectively]), but renal response was not significantly protective; conversely, the risk of ESRD was not significantly higher for the Kastritis renal progression, but was significantly protective for the Kastritis renal responders (HR 0.38 [95% CI: 0.17-0.84], p = .017). Both progression and response with ISA, Palladini and Kastritis criteria were predictive of ESRD at 6 months and 12 months. While the Palladini staging criteria at baseline, and the ISA and Palladini criteria for progression at 3 months performed better than the Kastritis criteria at baseline and 3 months post-treatment, the Kastritis criteria performed better for response 3 months after treatment. All three sets of criteria performed well at and after 6 months post-treatment. These differences are important when choosing endpoints for clinical trials.

Prognostic Role of Beta-2 Microglobulin in Patients with Light Chain Amyloidosis Treated with Autologous Stem Cell Transplantation.

The prognostic impact of increased beta-2 microglobulin (B2M) in patients with light chain (AL) amyloidosis undergoing autologous stem cell transplantation (ASCT) is unknown. The Mayo 2012 stage and increased bone marrow plasma cell (BMPC) percentage are known predictors for survival. Increased B2M is predictive of survival in patients with multiple myeloma. We evaluated the prognostic role of B2M in patients with newly diagnosed AL undergoing ASCT. We retrospectively reviewed patients with a diagnosis of AL amyloidosis who were treated with ASCT between July 1996 and September 2017. Patients with a creatinine level >1.2 mg/dL were excluded, because that affects B2M levels. The receiver operator characteristic curve was used to determine the best cutoff for B2M before ASCT in predicting survival, which was 2.5 µg/mL, which was also the upper limit of normal in our laboratory. Baseline characteristics were compared between patients with B2M >2.5 µg/mL and ≤2.5 µg/mL. Progression-free survival (PFS) was defined as the time from ASCT to relapse or death, whichever occurred first. Overall survival (OS) was calculated from the time of ASCT to death of any cause. Univariate and multivariate analyses were done for OS. Five hundred and ten patients were identified, 222 of whom (44%) had a B2M >2.5 µg/mL. These patients were more likely to be older (median age, 61 versus 57 years; P = .0002), to have Mayo 2012 stage III/IV disease (33% versus 8%; P < .0001), to have more than 2 organs involved (25% versus 14%; P = .001), and to have ≥10% BMPCs (56% versus 40%; P = .0002) compared with patients with B2M ≤2.5 µg/mL. The median PFS and OS were shorter in patients with B2M >2.5 µg/mL (median PFS, 64 months versus 80 months [P = .03]; median OS, 104.9 months versus 175.5 months [P < .0001]). On univariate analysis, predictors for OS included age >60 years (hazard ratio [HR], 1.61; P = .001), Mayo 2012 stage III/IV (HR, 3.36; P < .0001), more than 2 organs involved (HR, 1.36; P = .07), ≥10% BMPCs (HR, 1.5; P = .005), melphalan conditioning with 200 mg/m2 (HR, .29; P < .0001), B2M >2.5 µg/mL (HR, 1.82; P < .0001), and transplantation during or after 2010 (HR, .4; P = .0006). On multivariate analysis, only Mayo 2012 stage III/IV (HR, 1.89; P = .005), melphalan conditioning with 200 mg/m2 (HR, .39; P < .0001), B2M >2.5 µg/mL (HR, 1.84; P = .003), and transplantation performed during or after 2010 (HR, .58; P = .03) remained independent predictors of OS. Our findings identify B2M >2.5 µg/dL before ASCT as an independent predictor for OS in patients with AL amyloidosis and normal kidney function and should be routinely measured.

Impact of minimal residual negativity using next generation flow cytometry on outcomes in light chain amyloidosis.

We evaluated bone marrow minimal residual disease (MRD) negativity in 44 patients with light chain (AL) amyloidosis using next generation flow cytometry (sensitivity ≥1 × 10-5 ; median events analyzed: 8.7 million, range: 4.8 to 9.7 million). All patients underwent MRD testing in 2 years from start of therapy (median: 7 months). The overall MRD negative rate was 64% (n = 28). The MRD-negative rate after one-line of therapy was 71% (20/28). And, MRD negative rates were higher with stem-cell transplant as first-line therapy (86%, 18/21) vs chemotherapy alone as first-line treatment (29%, 2/7), P = .005. The MRD negative rate amongst patients in complete response was 75% (15/20), and in very good partial response, 50% (11/22). There were two patients in partial response/rising light chains (with renal dysfunction) who were MRD negative. There were no differences in baseline characteristics of MRD negative vs MRD positive patients, except younger age amongst MRD-negative patients. Patients with MRD negativity were more likely to have achieved cardiac response at the time of MRD assessment, 67% (8/12) vs 22% (2/7), P = .04. Renal response rates were similar in both groups. Progression free survival was assessed in the 42 patients achieving CR or VGPR. After median follow-up of 14 months, the estimated 1-year progression free survival in MRD negative vs MRD positive patients was 100% (26 patients, 0 events) vs 64% (16 patients, five events), P = .006, respectively. MRD assessment should be explored as a surrogate endpoint in clinical trials and MRD risk-adapted trials may help optimize treatment in AL amyloidosis.

Hematopoietic score predicts outcomes in newly diagnosed multiple myeloma patients.

Risk stratification of multiple myeloma (MM) at diagnosis is critical. We examined the ability of hematopoietic indices including mean corpuscular volume (MCV), hemoglobin (Hgb), and platelet (Plt) to predict outcomes. This was a retrospective study of patients treated at Mayo Clinic between January 2004 and April 2018. We incorporated three variables (Hgb < 10 g/dL, Plt < 150 × 109 /L, and MCV > 96 fL), assigning a score of 1 to each. We identified 1540 newly diagnosed MM patients, of whom 707 (46%) had a score of 0, 513 (33%) had a score of 1, 260 (17%) had a score of 2, and 60 (4%) had a score of 3. The score risk stratified patients into four groups with differing survivals. The median PFS was 32.3 months for score 0, 24.8 months for score 1, 21.7 months for score 2, and 18.3 months for score 3, for P < .001. The median OS was 80.7 months for score 0, 59.9 months for score 1, 51.7 months for score 2, and 31.3 months for score 3, P < .0001. Predictors of OS on the multivariable analysis were age ≥ 65 (HR, 1.93; P < .0001), R-ISS stage (1-2 vs 3) (HR, 0.48; P < .0001), and hematopoietic score (0-2 vs 3) (HR, 0.51; P = .006). A hematopoietic score can predict survival in newly diagnosed myeloma patients.

The Human Microbiota in Multiple Myeloma and Proteasome Inhibitors.

The gut microbiota plays a significant role in health and disease, including cancer development and treatment. The importance of the gut microbiota in the efficacy and toxicity of novel therapies and immunotherapy is increasingly recognized. Plasma cells in multiple myeloma have the potential to survive in the gastrointestinal tract for long periods of time. The nature of the gut microbiota impacts the degree of antigen stimulation of these cells and may play a role in mutation development and clonal evolution. Furthermore, myeloma therapies such as proteasome inhibitors and alkylating agents, commonly used to treat patients, are frequently associated with gastrointestinal adverse events. Herein we review the gut microbiota and its role in hematopoiesis, pathogenesis of myeloma, and efficacy/toxicity of anti-myeloma therapies.

Autologous Stem Cell Transplant for IgM-Associated Amyloid Light-Chain Amyloidosis.

IgM-related amyloid light-chain (AL) amyloidosis is a rare disease, with patients presenting with more renal and neurologic involvement and less cardiac involvement compared with those with non-IgM-related disease. We retrospectively reviewed 38 patients receiving autologous stem cell transplant (ASCT) for IgM-related AL amyloidosis at the Mayo Clinic between May 1999 and June 2018. Median age was 61years, and 71% were men. The most common organs involved were renal (63%), neurologic (32%), and cardiac (26%). The median difference between involved and uninvolved free light chains was 6.2mg/dL, and most patients had early Mayo stage disease (87% Mayo stage I 2004 and 74% Mayo stage I 2012). The overall response rate was 92%, with 76% of patients achieving at least a very good partial response. Renal response was seen in 65% of patients (15/23; median time, 18 months post-ASCT; range 3 to 52) and cardiac response in 60% of patients (6/10; median time, 12 months post-ASCT; range 10 to 35). Median progression-free survival (PFS) and overall survival (OS) was 48 and 106 months, respectively. Organ response predicted better PFS and OS (median PFS, 93 months for organ response versus 16 months for no organ response [P = .0006]; and median OS, 123 months for organ response versus 41 months for no organ response [P = .02]). Two patients died within 100days of transplant, representing a 5% 100-day mortality. ASCT is an effective therapy that can be safely delivered to carefully selected patients with IgM-related AL amyloidosis.

Outcomes of Patients with Light Chain Amyloidosis Who Had Autologous Stem Cell Transplantation with 3 or More Organs Involved.

Prior reports have suggested that 3 or more organs involved is a contraindication for autologous stem cell transplant (ASCT) in amyloid light chain (AL) amyloidosis. Therefore, most centers limit transplantation to patients who have no more than 2 organs significantly involved. We retrospectively reviewed all patients with AL amyloidosis with ≥3 involved organs and who had ASCT between 1996 and 2015 at Mayo Clinic, Rochester, Minnesota to assess transplant safety and outcomes. Seventy-five patients with ≥3 organs involved underwent ASCT. Median age at diagnosis was 54 years, and 67% were men. The heart was involved in 95%, followed by the kidneys (84%). Thirty-eight patients (51%) had no induction treatment before ASCT. Full-dose melphalan (200 mg/m2) was given in 45%, and the remainder received 140 mg/m2. Overall hematologic response rate was 75%. The median progression-free survival (PFS) and overall survival (OS) were 16 and 68 months, respectively. The 100-day mortality was 16%, and 44 patients (59%) died during follow-up. The most common causes of death were cardiovascular events (32%) and progressive amyloidosis (25%). On multivariable analysis, predictors for PFS were Mayo 2012 stage III/IV (relative risk [RR], 3.3; P = .0012) and hematologic response (at least very good partial response; RR, .4; P = .012). An N-terminal pro-brain natriuretic peptide (NT-proBNP) level of ≥2000 pg/mL was an independent predictor for shorter PFS (RR, 2.6; P = .013). Predictors for OS included any hematologic response (RR, .12; P = .0015), melphalan 200 mg/m2 (RR, .2; P = .014), and Mayo 2012 stage III/IV (RR, 7.7; P = .0002). An NT-proBNP level ≥ 2000 pg/mL was a powerful predictor of OS (RR, 4; P = .013). The number of organs involved (3 versus >3) did not significantly impact PFS or OS. We conclude that the high prevalence and severity of cardiac involvement are the main drivers for the poor outcome in patients who have ≥3 organs involved. Using selection criteria defined for safe transplantation in cardiac amyloidosis should result in low therapy-related mortality independent of the number of organs involved. The severity of cardiac involvement should be the major criterion for transplanting patients with AL amyloidosis that have ≥3 organs involved and not merely the number of organs involved.

Impact of consolidation therapy post autologous stem cell transplant in patients with light chain amyloidosis.

The role of consolidation post autologous stem cell transplant in light chain amyloidosis is not well defined. We retrospectively identified patients who had light chain amyloidosis and underwent autologous stem cell transplant at the Mayo Clinic. Consolidation was defined as any treatment given after the day 100 evaluation post-transplant to maintain or deepen the response. We identified 471 patients, of whom 72 (15%) received consolidation. Patients receiving consolidation had more advanced disease (Mayo 2012 stage ≥II in 67% vs 52%, P = .02), and had lower day 100 response rates (very good partial response or better: 35% vs 84%, P < .001). After consolidation, rates of very good partial response improved from 24% to 28%, and rates of complete response improved from 11% to 40%. Patients with less than very good partial response who received consolidation, had better progression-free survival (median of 22.4 vs 8.8 months, P < .001), and the benefit was greater in those who deepened their response (median of 41 vs 8.8 months, P < .001). In patients with less than very good partial response, there was a trend for better overall survival in patients who responded to consolidation (median of 125.8 vs 74.4 months, P = .07). In patients who achieved very good partial response, or better, at day 100 post autologous stem cell transplant, consolidation did not improve progression-free or overall survival. Consolidation after autologous stem cell transplant for light chain amyloidosis improves progression-free survival for patients who achieve less than very good partial response.

Fifteen year overall survival rates after autologous stem cell transplantation for AL amyloidosis.

In appropriately selected patients with AL amyloidosis, autologous stem cell transplant (ASCT) is an established treatment modality with excellent outcomes and decreasing transplant related mortality (TRM) over time. We report on 15-year overall survival (OS) in 159 patients undergoing ASCT from 1996 to 2003, with median follow up of 17.1 years. Day 100 TRM was 13.2% (n = 21). The OS of ≥15 years was observed in 30% (47/159) of patients. Patients surviving ≥15 years were younger (53 vs 56 years, P = .02), less likely to have lambda as the involved light chain (62% vs 78%, P = .03) and were less likely to have heart involvement (32% vs 56%, P = .005). Median OS of patients with heart involvement vs not was 4.0 vs 11.1 years, P = .006 and actuarial 15-year OS was 23% vs 43%, respectively. A higher proportion of patients with OS ≥15 years received full-dose melphalan conditioning (81% vs 61%, P = .01), and achieved day 100 complete response (CR) (64% vs 24%, P < .001). Median OS amongst patients who achieved CR vs not was 19.3 vs 5.4 years, P < .001. Heart involvement, receiving full-dose melphalan and achieving CR remained independent predictors of OS. AL amyloidosis and related complications were the cause of death in 52% of patients overall (1-5 years post-transplant: 81%; 5-10 years: 62% and 10-15 years: 55%). These results reinforce the key role of ASCT in AL amyloidosis. With improvements in TRM and more options for relapsed disease, we expect the long-term survival post-transplant to improve significantly in the future.

Prognostic Significance of Stringent Complete Response after Stem Cell Transplantation in Immunoglobulin Light Chain Amyloidosis.

Hematologic response has emerged as a powerful prognostic factor for survival in patients with immunoglobulin light chain (AL) amyloidosis. Patients achieving a complete response (CR), based on serum and urine analysis, survive longest. However, data regarding the impact of bone marrow features post-therapy on response and survival are limited. We evaluated the impact of achieving a stringent CR (sCR), defined as undetectable bone marrow clonal plasma cells by flow cytometry, in patients with AL amyloidosis receiving an autologous stem cell transplant. A total of 573 consecutive patients transplanted for AL amyloidosis at the Mayo Clinic between April 2002 and August 2016 were included in the analysis. Of 540 patients in whom response was assessable, 220 patients (41%) achieved a CR, of whom 212 (96%) had a bone marrow biopsy at time of response assessment and were further analyzed for determination of sCR; 166 patients (78%) with a CR achieved an sCR, representing 31% of the whole cohort. Patients achieving a CR had a higher median percentage of bone marrow plasma cells (10% for CR versus 6% for sCR, P = .03), more patients with bone marrow plasma cells ≥ 10% (50% for CR versus 33% for sCR, P = .04), and were less likely to receive chemotherapy before transplantation (30% for CR versus 49% for sCR, P = .03) compared with those achieving sCR. Median overall survival for all patients achieving a CR was 175 months and was not statistically different between those achieving an sCR compared with those achieving a CR only (median not reached for sCR versus 175 months for CR, P = .65). Progression-free survival, however, was significantly shorter in patients failing to achieve an sCR (151 months for sCR versus 72 months for CR, P = .0003). Bone marrow examination post-transplant in AL amyloidosis is important and identifies patients who fail to achieve an sCR and progress earlier.

Autologous Stem Cell Transplant for Immunoglobulin Light Chain Amyloidosis Patients Aged 70 to 75.

Autologous stem cell transplantation (ASCT) has been used in treatment for immunoglobulin light chain (AL) amyloidosis for over 2 decades and is generally reserved for patients younger than 70 years. Herein we report on outcomes of ASCT in a cohort of patients with AL amyloidosis aged 70 years or older. Between August of 2002 and April of 2017, 34 patients aged 70 years or older, with biopsy-proven AL amyloidosis, received an ASCT at the Mayo Clinic Rochester. Seventy percent of patients (n = 24) were transplanted within 6 months of diagnosis, and 74% (n = 25) received reduced-intensity conditioning with melphalan <200 mg/m2. Sixty-five percent of patients (n = 22) required hospitalization with a median duration of hospital admission of 8 days. Common reasons for hospitalization included fever or infection (14%), cardiac arrhythmia (14%), nutritional support (24%), and volume overload (19%). Overall response rate was 75%, with a complete response seen in 25% of patients. Overall survival and progression-free survival for the cohort were 66 months and 40 months, respectively. One patient died within 100 days of transplant, representing a 3% 100-day mortality rate. ASCT is safe and efficacious in carefully screened patients aged 70 or above.

Plasma cell proliferative index predicts outcome in immunoglobulin light chain amyloidosis treated with stem cell transplantation.

The plasma cell proliferative index provides an insight into plasma cell biology in plasma cell disorders and is an important prognostic marker in myeloma and smoldering myeloma. We analyzed the prognostic impact of the plasma cell proliferative index in 513 patients with systemic immunoglobulin light chain (AL) amyloidosis undergoing stem cell transplantation at the Mayo Clinic between 1st January 2003 and 31st August 2016. Two cohorts were identified according to Low or Elevated plasma cell proliferative index. Patients with an Elevated plasma cell proliferative index had more cardiac involvement (56% vs 44%; P=0.01), less renal involvement (55% vs 70%; P=0.001), and were more likely to have 10% or over bone marrow plasma cells (58% vs 32%; P<0.0001) compared to those with a Low plasma cell proliferative index. Both progression-free survival and overall survival were lower in patients with an Elevated compared to Low plasma cell proliferative index: median progression-free survival 44 vs 95 months (P<0.0001) and median overall survival 102 vs 143 months (P=0.0003). All-cause mortality at 100 days was higher in patients with an Elevated plasma cell proliferative index (elevated 10.3% vs low 4.3%; P=0.008). On multivariate analysis Elevated plasma cell proliferative index was an independent prognostic factor for overall survival (Hazard Ratio 1.5, 95%CI: 1.1-2.1; P=0.021). The plasma cell proliferative index is an important prognostic tool in patients with AL amyloidosis undergoing stem cell transplant.

Utility and prognostic value of 18 F-FDG positron emission tomography-computed tomography scans in patients with newly diagnosed multiple myeloma.

Positron emission tomography-computed tomography (PET-CT) can identify bony lesions, assess disease burden, and detect extramedullary disease (EMD) in patients with multiple myeloma. We retrospectively reviewed records of patients who underwent PET-CT within 60 days of a new diagnosis (before therapy commenced) to identify the nature and prognostic impact of PET-CT abnormalities. Patients (N = 313) were seen from April 2005 through June 2017. Of the 234 patients (75%) with focal lesions (FLs), 182 (58%) had at least 3 FLs, 38 (12%) had EMD, and 204 (65%) had documented myelomatous lytic lesions. The median maximum standardized uptake value (SUVmax ) for the entire cohort was 5.9 (range 1.5-48.3). Presence of at least 3 FLs and EMD predicted inferior overall survival (OS); median OS was 57.8 months for patients with 3 or more FLs and 103.6 months for patients with fewer than 3 FLs (P = .003). The median OS was 45.5 and 71.8 months for patients with and without EMD, respectively (P = .004). No clear SUVmax cutoff was predictive of progression-free survival or OS. PET-CT is a valuable tool for assessing disease burden and could provide prognostic information about a contemporary cohort of patients with newly diagnosed myeloma who received treatment with novel agents.

Imaging flow cytometric detection of del(17p) in bone marrow and circulating plasma cells in multiple myeloma.

BACKGROUND: Detection of del(17p) in myeloma is generally performed by fluorescence in situ hybridization (FISH) on a slide with analysis of up to 200 nuclei. The small cell sample analyzed makes this a low precision test. We report the utility of an automated FISH method, called "immuno-flowFISH", to detect plasma cells with adverse prognostic risk del(17p) in bone marrow and blood samples of patients with myeloma. METHODS: Bone marrow (n = 31) and blood (n = 19) samples from 35 patients with myeloma were analyzed using immuno-flowFISH. Plasma cells were identified by CD38/CD138-immunophenotypic gating and assessed for the 17p locus and centromere of chromosome 17. Cells were acquired on an AMNIS ImageStreamX MkII imaging flow cytometer using INSPIRE software. RESULTS: Chromosome 17 abnormalities were identified in CD38/CD138-positive cells in bone marrow (6/31) and blood (4/19) samples when the percent plasma cell burden ranged from 0.03% to 100% of cells. Abnormalities could be identified in 14.5%-100% of plasma cells. CONCLUSIONS: The "immuno-flowFISH" imaging flow cytometric method could detect del(17p) in plasma cells in both bone marrow and blood samples of myeloma patients. This method was also able to detect gains and losses of chromosome 17, which are also of prognostic significance. The lowest levels of 0.009% (bone marrow) and 0.001% (blood) for chromosome 17 abnormalities was below the detection limit of current FISH method. This method offers potential as a new means of identifying these prognostically important chromosomal defects, even when only rare cells are present and for serial disease monitoring.