Organ procurement organization compliance with 21 CFR 1271: a challenge for allogeneic pancreatic islet cell transplantation programs.

In order to protect tissue recipients, the Food and Drug Administration drafted Title 21, Section 1271 of the Code of Federal Regulations 1271 (21 CFR 1271) to address infectious disease risk. These regulations apply to tissues but not vascularized organs. Pancreatic islet cells are regulated under 21 CFR 1271. These regulations require qualification of suppliers of critical materials and services with regard to 21 CFR 1271 compliance. As part of supplier qualification, all organ procurement organizations (OPOs) in the United States were sent a questionnaire covering the key components of these regulations. Of the 57 OPOs, 29 (51%) were in compliance based upon survey results. Twelve (21%) were not compliant in one or more areas. All indicated plans to become compliant. The remaining 15 (27%) either failed or refused to complete the survey, some indicating 21 CFR 1271 did not apply to OPOs. Using 2006 data, OPOs compliant with 21 CFR 1271 recovered 50% of the organs procured in the United States. These findings represent a challenge for allogeneic islet cell transplant programs whose raw material must comply with 21 CFR 1271. OPOs should work toward understanding and complying with 21 CFR 1271. Regulatory agencies should work toward enhancing safety of the pancreas supply by facilitating compliance through harmonization of requirements.

Vancomycin-resistant enterococcal colonization appears associated with increased mortality among allogeneic hematopoietic stem cell transplant recipients.

There are no cohort studies describing outcomes of patients colonized with vancomycin-resistant enterococci (VRE) undergoing allogeneic hematopoietic stem cell transplantation (AHSCT). We therefore conducted a retrospective cohort study of 217 consecutive adults undergoing AHSCT at the Mayo Clinic (Rochester, MN, USA) from 1998 to 2004. We analyzed the association between VRE colonization prior to transplant and 100-day post transplant mortality and morbidity. We identified 22 pretransplant VRE colonized patients and 195 non-colonized patients. Both groups had similar baseline characteristics with the following six exceptions. Colonized patients were more likely to have had pretransplant Clostridium difficile-associated diarrhea, pretransplant acute renal failure, AML, Cy/TBI conditioning, decreased platelet count at time of transplantation and myeloablative conditioning regimens. Overall, patients colonized with VRE were twice as likely to die by day 100 post transplant compared to non-colonized patients (hazard ratio: 2.1, P=0.028). This association persisted even after adjusting for differences in baseline characteristics. Increased mortality in the colonized group correlated with the presence of VRE bacteremia. Overall, pretransplant VRE colonization appears to be an independent risk factor for increased mortality post-AHSCT.

Impact of lenalidomide therapy on stem cell mobilization and engraftment post-peripheral blood stem cell transplantation in patients with newly diagnosed myeloma.

While initial therapies have become highly effective with introduction of lenalidomide and bortezomib and patients may opt for delayed stem cell transplantation, it is important to collect stem cells for future transplant. Given its increasing use as initial therapy, we examined if lenalidomide had any impact on the ability to collect peripheral blood stem cells (PBSC). We studied the entire cohort of patients with myeloma undergoing PBSC mobilization at our institution during a 5-year period, comparing the results between patients receiving different initial therapies. Among those mobilized with granulocyte-colony stimulating factor (G-CSF) alone, there was a significant decrease in total CD34(+) cells collected (P<0.001), average daily collection (P<0.001), day 1 collection (P<0.001) and increased number of aphereses (P=0.004) in patients treated with lenalidomide compared to those receiving dexamethasone, thalidomide-dexamethasone or VAD. A similar trend was seen in those mobilized with chemotherapy and G-CSF. A trend was seen towards decreased PBSC yield with increasing duration of lenalidomide therapy as well as increasing age (P=0.002). There was no effect on quality of PBSC collected based on similar engraftment across all groups. We recommend collection of PBSC within 6 months of initiation of therapy with lenalidomide containing regimens to minimize the risk of mobilization failures.

Infrastructure development for human cell therapy translation.

The common conception of a drug is that of a chemical with defined medicinal effect. However, cells used as drugs remain critical to patient care. Cell therapy's origins began with the realization that complex tissues such as blood can retain function when transplanted to the patient. More complex transplantation followed, culminating with the understanding that transplantation of some tissues such as bone marrow may act medicinally. Administration of cells with an intended therapeutic effect is a hallmark of cellular therapy. While cells have been used as drugs for decades, testing a specific therapeutic effect of cells has begun clinical testing relatively recently. Lessons learned during the establishment of blood banking (including the importance of quality control, process control, sterility, and product tracking) are key components in the assurance of the safety and potency of cell therapy preparations. As more academic medical centers and private companies move toward exploiting the full potential of cells as drugs, needs arise for the development of the infrastructure necessary to support these investigations. Careful consideration of the design of the structure used to manufacture is important in terms of the significant capital outlay involved and the facility's role in achieving regulatory compliance. This development perspective describes the regulatory environment surrounding the infrastructure support for cell therapy and practical aspects for design consideration with particular focus on those activities associated with early clinical trials.

Impact of age and serum creatinine value on outcome after autologous blood stem cell transplantation for patients with multiple myeloma.

High-dose chemotherapy with stem cell transplantation (SCT) is feasible for elderly patients and patients with renal insufficiency. However, the impact of treatment on this patient population is unclear. We evaluated 678 consecutive patients with multiple myeloma who underwent SCT at Mayo Clinic. The complete response rate, time to progression and overall survival was recorded. Patients were stratified according to age (< or =65 or >65 years) and serum creatinine value at the time of transplantation (< or =2 or >2 mg/dl). Patient age did not have an effect on any outcome measure. Creatinine level did not affect complete response rate and time to progression, but patients with creatinine levels above 2 mg/ml had a higher day-100 mortality rate and a shorter overall survival rate. Platelet engraftment was also significantly delayed for patients with renal insufficiency. Selected patients over age 65 years may have outcomes identical to that of younger patients. When compared with patients with creatinine levels less than 2 mg/ml, patients with elevated creatinine levels had similar response rates and time to progression, but their overall survival was inferior. Transplantation should be offered to selected patients over age 65 years or selected patients with creatinine elevation.

Transplantation without growth factor: engraftment kinetics after stem cell transplantation for primary systemic amyloidosis (AL).

Stem cell transplantation is increasingly used in the management of immunoglobulin light-chain amyloidosis (AL). It is considered the standard of care to administer growth factors to accelerate neutrophil recovery after transplantation. However, unique toxicities occur with growth factor use in patients with AL who receive a stem cell transplant. We report a cohort of patients who underwent transplantation without receiving posttransplantation growth factors. In total, 282 patients received a stem cell transplant. A neutrophil count of 500/mul was achieved in 50, 75 and 90% of patients at 14, 16 and 22 days, respectively. A platelet count of 20 000/mul was achieved in 50, 75 and 90% of patients at 14, 20 and 31 days, respectively. Non-staphylococcal bacteremia was detected in 16% of patients. The median hospital stay was 9 days. It is feasible and reasonable to withhold growth factor therapy after autologous stem cell transplantation in patients with AL.

A phase 1 trial of 90Y-Zevalin radioimmunotherapy with autologous stem cell transplant for multiple myeloma.

This phase 1 study (clinical trial NCT00477815) was conducted to determine the maximum tolerated dose (MTD) of yttrium-90 ibritumomab tiuxetan (90Y-Zevalin) with high dose melphalan (HDM) therapy in multiple myeloma (MM) patients undergoing autologous stem cell transplantation (ASCT). In a 3+3 trial design, 30 patients received rituximab 250 mg/m2 with indium-111 ibritumomab tiuxetan (111In-Zevalin) for dosimetry (day -22); rituximab 250 mg/m2 with escalating doses of 90Y-Zevalin (day -14); melphalan 100 mg/m2 (days -2,-1) followed by ASCT (day 0) and sargramostim (GM-CSF, day 0) until neutrophil engraftment. Each patient's 111In-Zevalin dosimetry data were used to calculate the dose of 90Y-Zevalin (in mCi) to deliver 10, 12, 14, 16, 18 or 20 Gy to the liver. Dose limiting toxicities were seen in 3 patients. The overall response rate was 73% (22/30) with stringent complete response in 2 patients; complete response, 5; very good partial response, 12; and partial response, 3. The median PFS was 16.5 months and the median overall survival was 63.4 months. In MM, the MTD of 90Y-Zevalin with HDM is 18 Gy to the liver. The addition of radiation with novel delivery methods such as radioimmunotherapy combined with standard transplant regimens warrants further study.

Early lymphocyte recovery after autologous stem cell transplantation predicts superior survival in mantle-cell lymphoma.

Autologous stem cell transplantation (ASCT) is an effective treatment strategy for mantle-cell lymphoma (MCL) demonstrating significantly prolonged progression-free survival (PFS) when compared to interferon-alpha maintenance therapy of patients in first remission. The study of absolute lymphocyte count at day 15 (ALC-15) after ASCT as a prognostic factor in non-Hodgkin lymphoma (NHL) included different lymphoma subtypes. The relationship of ALC-15 after ASCT in MCL has not been specifically addressed. We evaluated the impact of ALC-15 recovery on survival of MCL patients undergoing ASCT. We studied 42 consecutive MCL patients who underwent ASCT at the Mayo Clinic in Rochester from 1993 to 2005. ALC-15 threshold was set at 500 cells/microl. The median follow-up after ASCT was 25 months (range, 2-106 months). The median overall survival (OS) and PFS times were significantly better for the 24 patients who achieved an ALC-15 >or=500 cells/microl compared with 18 patients with ALC-15 <500 cells/microl (not reached vs 30 months, P<0.01 and not reached vs 16 months, P<0.0006, respectively). Multivariate analysis demonstrated ALC-15 to be an independent prognostic factor for OS and PFS. The ALC-15 >or=500 cells/microl is associated with a significantly improved clinical outcome following ASCT in MCL.

Apheresis instrument settings influence infused absolute lymphocyte count affecting survival following autologous peripheral hematopoietic stem cell transplantation in non-Hodgkin's lymphoma: the need to optimize instrument setting and define a lymphocyte collection target.

Autograft absolute lymphocyte count (A-ALC) is an independent prognostic factor for survival after autologous peripheral blood hematopoietic stem cell transplantation (APHSCT) for non-Hodgkin's lymphoma (NHL). Factors enhancing A-ALC collections are unknown. We hypothesize that apheresis instrument settings could affect A-ALC. Data from 127 NHL patients collected from 15 January 1999 to 30 July 2004 using a single apheresis instrument (COBE Spectra (SP), Baxter Amicus (AM), and CS3000 Plus (CS)) were analyzed. The primary end point of the study was to assess the correlation between apheresis instrument settings and A-ALC. The secondary end point was to determine the effect of apheresis instrument on survival post-APHSCT. Patients collected using SP achieved higher A-ALC compared to AM (with modified settings) or CS (P<0.05) and demonstrated superior overall (OS) and progression-free survival (PFS) (P<0.03). Multivariate analysis demonstrated A-ALC and not the apheresis instrument as an independent prognostic factor for OS and PFS, cancelling the prognostic effect of the apheresis instruments observed in the univariate analysis. The survival advantage observed by SP was from the higher A-ALC collected compared to AM and CS. These data suggest that apheresis instrument settings should be optimized to collect CD34(+) cells as well as an A-ALC target, with direct impact on survival post-APHSCT.

Autologous hematopoietic stem cell transplantation for older patients with relapsed non-Hodgkin's lymphoma.

To evaluate autologous stem cell transplant (ASCT) in older patients with intermediate grade non-Hodgkin's lymphoma (NHL), the Mayo Clinic Rochester BMT database was reviewed for all patients 60 years of age and older who received ASCT for NHL between September 1995 and February 2003. Factors evaluated included treatment-related mortality (TRM), event-free survival (EFS) and overall survival (OS). Ninety-three patients were identified, including twenty-four (26%) over the age of 70 years. Treatment-related mortality (5.4%) was not significantly different when compared to a younger cohort (2.2%). At a median follow-up of 14 months (0.6-87.6 months), the estimated median survival is 25 months (95% confidence interval (CI) 12-38) in the older group compared to 56 months (95% CI 37-75) (P=0.037) in the younger group. The estimated 4-year EFS was 38% for the older group compared to 42% in the younger cohort (P=0.1). By multivariate analysis, the only factor found to influence survival in the older group was age-adjusted International Prognostic Index at relapse, 0-1 better than 2-3 (P=0.03). Autologous stem-cell transplant can be safely performed in patients 60 years or older with chemotherapy sensitive relapsed or first partial remission NHL. The outcome may not be different from that of younger patients in terms of TRM and EFS.

Allogeneic stem cell transplantation and donor lymphocyte infusions for chronic myelomonocytic leukemia.

Prognosis in chronic myelomonocytic leukemia (CMML) is unfavorable and the optimal therapy remains uncertain. Currently, allogeneic stem cell transplantation is the only known curative therapeutic option. However, the data available are limited and restricted to small retrospective series. There is even less information on the use of donor lymphocyte infusions (DLI) for this disease. We reviewed our experience of allogeneic stem cell transplantation and DLI for adults with CMML. Seventeen consecutive adults underwent allogeneic stem cell transplantation from related (n=14) or unrelated (n=3) donors. Median age was 50 years (range 26-60). Seven patients (41%) demonstrated relapse or persistent disease at a median of 6 months (range 3-55.5). Five patients underwent DLI for morphologic relapse and one for mixed donor chimerism. Two patients achieved durable complete remissions of 15 months each. The overall transplant-related mortality was 41% (n=7). With a median follow-up of 34.5 months, three patients (18%) currently remain alive and in continuous CR. The current study demonstrates a graft-versus-leukemia effect in CMML, both for allogeneic stem cell transplantation and for DLI. Nevertheless, consistent with reported experience of others, overall outcomes remain less than optimal and unpredictable.

A phase I study of 153Sm-EDTMP with fixed high-dose melphalan as a peripheral blood stem cell conditioning regimen in patients with multiple myeloma.

Despite response rates of 30% after high-dose chemotherapy with autologous hematopoietic stem cell transplant, patients with multiple myeloma are not cured. 153Samarium ethylenediaminetetramethylenephosphonate (153Sm-EDTMP; Quadramet) is a short-range, beta-emitting therapeutic radiopharmaceutical with avid skeletal uptake. In total, 12 patients were treated with escalating doses of 153Sm-EDTMP (N=3/group; 6, 12, 19.8, and 30 mCi/kg) and a fixed dose of melphalan (200 mg/m(2)). No dose limiting toxicity was seen. To better standardize the marrow compartment radiation dose, the study was modified such that an additional six patients were treated at a targeted absorbed radiation dose to the red marrow of 40 Gy based on a trace labeled infusion 1 week prior to the therapy. Despite rapid elimination of unbound radiopharmaceutical via kidneys and bladder, no episodes of nephrotoxicity, hemorrhagic cystitis, or delayed radiation nephritis were observed with a median follow-up of 31 months (range 8.5-44). Median times to ANC>0.5 and platelet >20 x 10(6)/l were 12 and 11 days, respectively, with no graft failures. Overall response rate was 94% including seven very good partial responses and five complete responses. Addition of 153Sm EDTMP to melphalan conditioning appears to be safe, well-tolerated and worthy of further study.

Autologous stem cell transplant for multiple myeloma patients 70 years or older.

Autologous stem cell transplant (Auto-SCT) is increasingly used in older patients with multiple myeloma (MM), despite lack of phase 3 trials in this age-defined population. For 207 consecutive MM patients who underwent Auto-SCT and were 70 years or older at transplant (study cohort), data were analyzed and compared with a younger cohort (1764 Auto-SCT patients <70 years old). The proportion of Auto-SCT in the older patients increased from 7.8% of all transplants in 1998-2006 to 12.9% in 2007-2015. Sixty percent of patients required stem cell mobilization with chemotherapy or plerixafor. Full-dose melphalan conditioning was given to 55% of the older patients compared with 93% of the younger patients (P<0.001). Older patients were more likely to be hospitalized (64% vs 55%; P=0.01), but hospitalization duration was comparable. For newly diagnosed patients, median PFS was 33.5 months for the older cohort and 33.8 months for the younger cohort (P=0.91), and median overall survival was 6.1 and 7.8 years, respectively (P=0.11). Presumably, a smaller fraction of patients, age 70-76, is selected for Auto-SCT, but the benefits are comparable to those seen for younger patients. Reduced-dose melphalan was given to approximately half the patients to avoid excessive toxicity.

Isolation of human platelet and red blood cell plasma membrane proteins by preparative detergent electrophoresis.

High resolution polyacrylamide gel electrophoretic techniques have been applied to the preparative isolation and analysis of plasma membrane proteins and glycoproteins from human platelets and red blood cells. The techniques presented allow relatively simple, direct, rapid and quantitative purification of a broad molecular weight range of membrane proteins, by means of continuous elution preparative gel electrophoresis of protein solubilized with sodium dodecyl sulfate. Spectrophotometric and fluorophotometric (fluorescamine) profiling, and high resolution gel electrophoretic analysis (SDS-acrylamide gradient slab gels, and gel electrofocusing) of eluted protein species indicate that purified membrane proteins of a broad molecular weight range may be obtained in a one step procedure, and in quantities and concentrations sufficient for further analytical or experimental procedures.

Lymphocyte recovery after allogeneic bone marrow transplantation predicts risk of relapse in acute lymphoblastic leukemia.

Allogeneic blood and marrow transplantation (BMT) is curative for many patients with high-risk and relapsed acute lymphoblastic leukemia (ALL). However, relapse is an important cause of post-transplantation failure, and there are no reliable markers to predict relapse. A retrospective review of patients with ALL who underwent matched related allogeneic BMT was carried out to examine whether the rate of lymphocyte recovery after transplantation had any prognostic value in ALL. The absolute lymphocyte count (ALC) at days 21 and 30 after transplantation was obtained for 43 patients who received transplants during an 18-year period. Patients with an ALC of 175 x 10(6)/l or less on day 21 were more likely to relapse than those with ALC greater than 175 x 10(6)/l (relative risk, 4; 95% confidence interval, 1.5-11.2). Patients with slower lymphocyte recovery had significantly lower relapse-free survival than those with faster recovery (P=0.0028). There was also a trend toward poorer overall survival among those with a slow lymphocyte recovery (log-rank test; P=0.028). The rate of lymphocyte recovery is prognostic in patients with ALL undergoing allogeneic BMT, and this should be integrated with other predictors to identify patients at high risk of relapse. Such patients could be considered for interventions aimed at prevention of relapse, including rapid withdrawal of immunosuppressive medication or donor lymphocyte infusion.

The dose of infused lymphocytes in the autograft directly correlates with clinical outcome after autologous peripheral blood hematopoietic stem cell transplantation in multiple myeloma.

Absolute lymphocyte count at day 15 (ALC-15) after autologous peripheral blood hematopoietic stem cell transplantation (APHSCT) is an independent prognostic factor for survival in multiple myeloma (MM); however, factors affecting ALC-15 in MM remain unknown. We hypothesized that the dose of infused peripheral blood autograft lymphocytes (autograft absolute lymphocyte count: A-ALC) impacts ALC-15 recovery. Between 1989 and 2001, 267 consecutive MM patients underwent APHSCT. We set out to determine the correlation between A-ALC and ALC-15 and the utility of A-ALC as a marker for ALC-15 recovery. A-ALC was found to be both a strong predictor for area under curve (AUC=0.93; P=0.0001) and strongly correlated with (r(s)=0.83; P=0.0001) ALC-15 recovery. Higher infused A-ALC was significantly correlated with an ALC-15>/=500/microl. In addition, median post-transplant overall survival (OS) and time to progression (TTP) were longer in patients who received an A-ALC>/=0.5 x 10(9) lymphocytes/kg versus A-ALC <0.5 x 10(9) lymphocytes/kg (58 vs 30 months, P=0.00022; 22 vs 15 months, P<0.00012, respectively). Multivariate analysis demonstrated A-ALC as an independent prognostic indicator for OS and TTP. These results indicate that an infused dose of autograft lymphocytes significantly impacts clinical outcome post-APHSCT in MM.

Priming tissue-specific cellular immunity in a phase I trial of autologous dendritic cells for prostate cancer.

We attempted to induce therapeutic immunity against prostate-derived tissues in patients suffering from progressive hormone-refractory metastatic prostate carcinoma. Thirteen patients were treated with two infusions, 1 month apart, of autologous dendritic cells (APC8015) preexposed ex vivo to PA2024, a fusion protein consisting of human granulocyte/macrophage-colony stimulating factor (GM-CSF) and human prostatic acid phosphatase (PAP). The infusions were followed by three s.c. monthly doses of PA2024 without cells. Three groups of patients each received PA2024 at 0.3, 0.6, or 1.0 mg/injection. All Ps were two-sided. Treatment was well tolerated. After infusions of APC8015, patients experienced only mild (grade 1-2) short-lived fever and/or chills, myalgia, pain, and fatigue. One patient developed grade 3 fatigue. Four patients developed mild local reactions to s.c. PA2024. Twelve patients were evaluable for response to treatment. Circulating prostate-specific antigen levels dropped in three patients. T cells, drawn from patients after infusions of APC8015, but not before, could be stimulated in vitro by GM-CSF (P = 0.0004) and PAP (P = 0.0001), demonstrating broken immune tolerance against these two normal proteins. Injections of PA2024 did not influence the reactivity of T cells against PAP and GM-CSF. However, antibodies to GM-CSF and, to a much lesser extent, to PAP reached maximum titers only after two or even three injections of PA2024, showing that directly injected PA2024 was involved in stimulation of humoral immunity. Dendritic cells exposed to antigen ex vivo can induce antigen-specific cellular immunity in prostate cancer patients, warranting further studies of this mode of immunotherapy.

Paroxysmal nocturnal hemoglobinuria as a marker for clonal myelopathy.

Paroxysmal nocturnal hemoglobinuria (PNH) is recognized as a clonal disorder manifested as increased sensitivity of marrow cells to complement. Case reports have associated this condition with leukemia, myelodysplasia, and myeloproliferative disorders. We identified 47 patients with PNH from 1976 to 1990. In 9 of the 47 patients, PNH was associated with another clonal myelopathy. Five patients had PNH and a myelodysplastic syndrome, and four had PNH and agnogenic myeloid metaplasia. PNH preceded the development of myelodysplastic syndrome but occurred after the development of agnogenic myeloid metaplasia. This is the largest series of PNH and other clonal myelopathies. We suggest that the PNH defect may represent a second manifestation of a single stem cell disorder.

Relapsing hairy cell leukemia presenting as fulminant hepatitis.

PURPOSE: We report the first known case of fulminant hepatitis due to hairy cell infiltration. CASE REPORT: A 43-year-old woman with hairy cell leukemia returned 1 year after diagnosis with spider angiomata of the face and neck, palmar erythema, and diffuse telangiectasias. The liver span was normal. Laboratory studies included: aspartate aminotransferase, 56 U/L; alkaline phosphatase, 283 U/L; gamma-glutamyltransferase, 157 U/L; and normal bilirubin. A liver biopsy demonstrated modest infiltration of hairy cells with hemosiderosis and intact hepatocytes. RESULTS: The patient responded to interferon-alpha with resolution of the angiomata, decreased palmar erythema, and improved liver function tests. Five months later, she presented with right upper quadrant pain, anorexia, fatigue, and diffuse myalgias. The physical examination was unchanged. Laboratory studies included: aspartate aminotransferase, 299 U/L; alkaline phosphatase, 1,388 U/L; total bilirubin, 43 mumol/L; and direct bilirubin, 29 mumol/L. Two weeks later, she was admitted to the hospital. Her liver span was 15 cm. Laboratory studies showed the following values: aspartate aminotransferase, 618 U/L; alkaline phosphatase, 2,319 U/L; total bilirubin, 311 mumol/L; direct bilirubin, 233 mumol/L; and alanine aminotransferase, 462 U/L. Intensive investigation of contributing causes was not revealing. A subsequent liver biopsy demonstrated extensive portal and intralobular hairy cell infiltration with loss of normal architecture. Liver function deteriorated as shown by the following values: aspartate aminotransferase, 1,100 U/L; alkaline phosphatase, 3,645 U/L; bilirubin, 477 mumol/L; and ammonia, 47 mumol N/dL. The patient died 9 days after admission. CONCLUSIONS: Although liver infiltration is often present and mild elevations of liver function tests have been noted, evidence of such extensive hepatic injury caused by hairy cell leukemia has not been reported previously. Hairy cell infiltration of the liver can cause typical cutaneous changes of liver disease and even fulminant hepatitis.

POEMS syndrome with idiopathic flushing mimicking carcinoid syndrome.

POEMS syndrome, a rare multisystem disease, is a variant of osteosclerotic myeloma and is characterized by polyneuropathy, organomegaly, endocrinopathy, monoclonal proteins, and skin changes. Presented herein is a case of POEMS syndrome with flushing. The flushing was intermittent, involving the face and upper third of the trunk, and was associated with hypotension and bronchospasm. Final diagnosis was made by biopsy examination of an axillary lymph node, which showed angiofollicular hyperplasia that stained strongly and selectively for lambda light chains. The patient had most of the typical features of POEMS syndrome but was unique in that her most striking finding was carcinoid-like flushing. The flushing improved with steroid therapy, as did some of the other clinical features of her disease. This case suggests that idiopathic flushing can be added to the skin changes observed in POEMS syndrome.