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Morie A Gertz

Publications and source records attributed to Morie A Gertz.

At least 19 recordsLinked to original sources
PubMed2007

Globular amyloid deposits isolated to the small bowel: a rare association with AL amyloidosis.

We describe a 55-year-old man with isolated duodenal and jejunal amyloidosis producing rare endoscopic and histologic findings. The patient had no specific gastrointestinal complaints but underwent esophagogastroduodenoscopy and colonoscopy because of progressive microcytic anemia. Endoscopy revealed multiple polyps, some filiform and measuring up to 3 cm in length, in the duodenum and proximal jejunum. Microscopically, the polyps resulted from amyloid deposition, predominantly within the submucosa, but also focally involving muscularis mucosae and lamina propria. The amyloid formed multiple globular submucosal deposits with a lamellated appearance reminiscent of corpora amylacea; linear amyloid deposition was also present in a perivascular distribution and within the overlying mucosa. Immunophenotyping confirmed AL amyloidosis with lambda immunoglobulin light chain restriction. There was no clinical evidence of visceral amyloidosis. The source of lambda light chain production was unclear as bone marrow biopsy and multiple gastrointestinal biopsies revealed normal numbers of polyclonal plasma cells. Further, immunoglobulin-free light chain assay was normal, as were serum and urine protein electrophoreses with immunofixation. This endoscopic presentation of isolated small bowel polyposis is an uncommon association with AL amyloidosis and to our knowledge this represents the first case of globular gastrointestinal amyloidosis resulting from AL amyloid.

Amyloid↗
PubMed2006

Novel analysis of clonal diversification in blood B cell and bone marrow plasma cell clones in immunoglobulin light chain amyloidosis.

Immunoglobulin light chain amyloidosis (AL) is characterized by a limited clonal expansion of plasma cells and amyloid formation. Here, we report restriction in the diversity of VL gene usage with a dominance of clonally related B cells in the peripheral blood (PB) isotype-specific repertoire of AL patients. A rigorous quantification of lineage trees reveals presence of intraclonal variations in the PB clones compared to the bone marrow (BM) clones, which suggests a common precursor that is still subject to somatic mutation. When compared to normal BM and PB B cells, AL clones showed significant but incomplete impairment of antigenic selection, which could not be detected by conventional R and S mutation analysis. Therefore, graphical analysis of B cell lineage trees and mathematical quantification of tree properties provide novel insights into the process of B cell clonal evolution in AL.

Algorithms↗
PubMed2006

The activity of lenalidomide with or without dexamethasone in patients with primary systemic amyloidosis.

Primary systemic amyloidosis (AL) is an incurable plasma cell disorder. Lenalidomide, especially in conjunction with dexamethasone, is highly active in patients with multiple myeloma. We studied the toxicity and efficacy of lenalidomide in patients with AL. Patients with symptomatic AL, a measurable plasma cell disorder, and adequate hematologic and renal reserve were eligible. Patients received single-agent lenalidomide. If there was no evidence of progression after 3 months or of hematologic response after 3 cycles, dexamethasone was added. Twenty-three patients were enrolled. Thirteen were previously treated. Organ involvement was cardiac (64%), renal (73%), hepatic (23%), and nerve (14%). Within the first 3 cycles of therapy, 10 patients discontinued treatment: 4 early deaths, 3 adverse events, and 3 other causes. With a median follow-up of 17 months, 10 patients responded to treatment. In these patients, responses included 9 hematologic, 4 renal, 2 cardiac, and 2 hepatic. All but one of the responders had dexamethasone added to their treatment program. The most common grade 3 or 4 adverse events at least possibly attributable to lenalidomide were neutropenia (45%), thrombocytopenia (27%), rash (18%), and fatigue (18%). In AL patients, we saw limited activity of single-agent lenalidomide, but significant activity of the combination with dexamethasone, which warrants further investigation.

Administration, Oral↗
PubMed2006

Gene-expression profiling of Waldenstrom macroglobulinemia reveals a phenotype more similar to chronic lymphocytic leukemia than multiple myeloma.

Waldenström macroglobulinemia (WM) is a B-cell malignancy characterized by the ability of the B-cell clone to differentiate into plasma cells. Although the clinical syndrome and the pathologic characteristics are well defined, little is known about its biology and controversy still exists regarding its cell of origin. In this gene-expression study, we compared the transcription profiles of WM with those of other malignant B cells including (chronic lymphocytic leukemia [CLL] and multiple myeloma [MM]) as well as normal cells (peripheral-blood B cells and bone marrow plasma cells). We found that WM has a homogenous gene expression regardless of 6q deletion status and clusters with CLL and normal B cells on unsupervised clustering with very similar expression profiles. Only a small gene set has expression profiles unique to WM compared to CLL and MM. The most significantly up-regulated gene is IL6 and the most significantly associated pathway for this set of genes is MAPK signaling. Thus, IL6 and its downstream signaling may be of biologic importance in WM. Further elucidation of the role of IL-6 in WM is warranted as this may offer a potential therapeutic avenue.

Antigens, CD↗
PubMed2006

Immunoglobulin free light chains and solitary plasmacytoma of bone.

An abnormal serum immunoglobulin free light chain (FLC) ratio at diagnosis may identify risk of progression to myeloma in patients with solitary bone plasmacytoma (SBP). In the cohort of 116 patients, 43 have progressed to myeloma, with a median time to progression of 1.8 years. The FLC ratio was determined in all 116 patients on serum collected at time of diagnosis and was abnormal in 54 patients (47%). An abnormal FLC ratio was associated with a higher risk of progression to myeloma (P = .039). The risk of progression at 5 years was 44% in patients with an abnormal serum FLC ratio at diagnosis compared with 26% in those with a normal FLC ratio. One to 2 years following diagnosis, a persistent serum M protein level of 5 g/L (0.5 g/dL) or higher was an additional risk factor for progression. A risk stratification model was constructed using the 2 variables of FLC ratio and M protein level: patients with a normal FLC ratio at baseline and M protein level less than 5 g/L (0.5 g/dL) at 1 to 2 years following diagnosis (low risk, n = 31); with either risk factor abnormal (intermediate risk, n = 26); and with both an abnormal FLC ratio and M protein level of 5 g/L (0.5 g/dL) or higher (high risk, n = 18). The corresponding progression rates at 5 years were significantly different in the low, intermediate, and high groups: 13%, 26%, and 62%, respectively (P < .001).

Adult↗
PubMed2006

Quantitative analysis of clonal bone marrow CD19+ B cells: use of B cell lineage trees to delineate their role in the pathogenesis of light chain amyloidosis.

Light chain amyloidosis (AL) is a bone marrow (BM) plasma cell neoplasia with systemic deposition of Ig light chain amyloid fibrils. Here, we report the identification of clonal CD19 B cells in the BM and the use of a novel mathematical algorithm to generate B cell lineage trees of the clonal CD19 B cells and CD138 plasma cells from the BM of AL patients to delineate the relationship between these two clonal populations. The CD19+ clonal B cells in the BM of AL patients related to the clonal plasma cells represent a pre-plasma cell precursor population. The B cell lineage trees from AL patients also show significant differences in clonal diversification and antigenic selection compared to clones from normal, healthy controls. These data provide a robust example of the use of graphical quantification methods in delineating the role of neoplastic precursors in the pathogenesis of hematopoietic malignancies.

Algorithms↗
PubMed2006

Flavopiridol in patients with relapsed or refractory multiple myeloma: a phase 2 trial with clinical and pharmacodynamic end-points.

Flavopiridol downregulates anti-apoptotic regulators including Mcl-1, upregulates p53, globally attenuates transcription through inhibition of P-TEFb, binds to DNA, and inhibits angiogenesis. Eighteen myeloma patients were treated with 1-hour flavopiridol infusions for 3 consecutive days every 21 days. Immunoblotting for Mcl-1, Bcl-2, p53, cyclin D, phosphoRNA polymerase II and phosphoSTAT 3 was conducted on myeloma cells. Ex vivo flavopiridol treatment of cells resulted in cytotoxicity, but only after longer exposure times at higher flavopiridol concentrations than were anticipated to be achieved in vivo. No anti-myeloma activity was observed in vivo. As administered, flavopiridol has disappointing activity as a single agent in advanced myeloma.

Aged↗
PubMed2006

Update on treatment recommendations from the Third International Workshop on Waldenstrom's macroglobulinemia.

Waldenström macroglobulinemia (WM) is a B-cell disorder characterized by the infiltration of lymphoplasmacytic cells into bone marrow and the presence of an IgM monoclonal gammopathy. As part of the Third International Workshop on WM, held October 7 to 10, 2004 in Paris, France, a consensus panel charged with providing treatment recommendations for WM updated its recommendations on both frontline and salvage therapies. The panel considered encouraging results from recent studies that addressed the use of extended-dose rituximab as well as other treatment options: therapy with either nucleoside analogs and alkylator agents, rituximab in combination with nucleoside analogs, nucleoside analogs plus alkylator agents, or combination chemotherapies, such as CHOP (cyclophosphamide, doxorubicin, vincristine, prednisone) or cyclophosphamide and dexamethasone. The panel determined that these were reasonable treatment options for WM patients and such therapeutic approaches were likely to yield results that are at least as good as if not better than the currently recommended use of single-agent alkylator, nucleoside analog, or standard-dose rituximab therapy. Such approaches were deemed to be reasonable treatment for WM patients in both the upfront and salvage settings, though randomized studies addressing the efficacy and toxicity of such novel approaches over previously established standard of care options are needed.

Alkylating Agents↗
PubMed2006

Absolute values of immunoglobulin free light chains are prognostic in patients with primary systemic amyloidosis undergoing peripheral blood stem cell transplantation.

The immunoglobulin free light chain (FLC) is the precursor protein of amyloid in primary systemic amyloidosis (AL). Historically, the ability to monitor the amyloid protein precursor protein has been crude. We evaluated the utility of the FLC assay in a retrospective analysis of patients with AL undergoing peripheral blood stem cell transplantation (PBSCT). Ninety-three such patients had serial FLC measurements performed. The prognostic effects of the initial concentration and the extent of reduction of monoclonal FLC on survival were studied. There was a significantly higher risk of death in patients with higher baseline FLC (hazard ratio 2.6, P < .04). Baseline FLC correlated with serum cardiac troponin levels, and higher FLC levels were associated with more organs involved by amyloid, suggesting that high FLC levels may be associated with more advanced disease. The percent FLC reduction did not predict for survival, but the absolute level of FLC achieved after therapy did. Normalization of FLC level after PBSCT predicted for both organ response and complete hematologic response. Achievement of FLC response was a better predictor of survival than achievement of complete hematologic response or normalization of the FLC ratio. FLC measurements both before and after PBSCT are important predictors of patient outcome.

Adult↗
PubMed2006

Natural history and therapy of 66 patients with mixed cryoglobulinemia.

Cryoglobulinemia, a relatively uncommon disorder, is classified into types I, II, and III, with type II consisting of a monoclonal immunoglobulin possessing activity toward a polyclonal component. Many disease associations and therapies have been described but clinical trials are few, and the natural history, causes, therapy, and pathways of cryoglobulinemia require further investigation. Here, we describe the symptoms, comorbidities, treatments, and response of 66 patients with type II cryoglobulinemia by examining the records of all patients evaluated at Mayo Clinic, Rochester, Minnesota, between 3/2/1994 and 11/27/2000, using our prospective dysproteinemia database. Symptoms varied greatly among patients and during the disease course. Most common were purpura (55% of patients), renal disease (26%), edema (24%), neuropathy (18%), and arthralgia (21%). Renal disease required the most aggressive intervention. Laboratory findings did not correlate with disease manifestations or severity. Only age was a significant predictor of mortality. Ten patients had cryoglobulinemia without an identified comorbidity. Thirty-three patients had viral hepatitis alone, 6 had a lymphoproliferative disorder alone, and 5 had a rheumatologic disease alone. Ten patients had a combination of disorders, such that hepatitis C was identified in a total of 40 patients, lymphoproliferative disorders in 16, and rheumatologic disease in 8. Twenty-two different treatments were administered. Corticosteroids were the most common treatment, followed by interferon with or without ribavirin. Type II cryoglobulinemia is a nonfatal disease most frequently associated with hepatitis C. Treatment is generally directed at the underlying condition. Not all patients require treatment, and many can be followed and treated symptomatically.

Adrenal Cortex Hormones↗
PubMed2006

Autologous or allogeneic stem cell transplantation in patients with Waldenstrom's macroglobulinemia.

The role of hematopoietic stem cell transplantation (SCT) in Waldenstrom's macroglobulinemia (WM) has not been extensively studied. To determine the potential for long-term disease control using SCT in WM, we performed a retrospective review of 36 patients with WM who received autologous (n = 10) or allogeneic (n = 26) SCT and were reported to the Center for International Blood and Marrow Transplant Research between 1986 and 2002. The following outcomes were described: nonrelapse mortality (NRM), relapse, progression-free survival (PFS), and overall survival (OS). Median age at the time of SCT was 51 years (range, 30-76 years), and median time from initial treatment to SCT was 29 months (range, 2-198 months). A total of 78% of the patients had 2 or more previous chemotherapy regimens, and 52% had disease resistant to salvage chemotherapy. In the allogeneic SCT group, 58% of the patients received myeloablative conditioning regimens containing total body irradiation (TBI), and of the allograft recipients, 19% received nonmyeloablative/reduced-intensity conditioning. After a median follow-up of 65 months, 15 of the 36 patients (42%) are alive. Primary disease accounted for 29% of the deaths in the allogeneic SCT group and 25% of the deaths in the autologous SCT group. The relapse rate at 3 years was 29% (95% confidence interval [CI], 14%-48%) in the allogeneic group and 24% (95% CI, 4%-54%) in the autologous group. PFS at 3 years was 31% (95% CI, 14%-50%) in the allogeneic group and 65% (95% CI, 32%-91%) in the autologous group; OS was 46% (95% CI, 27%-65%) in the allogeneic group and 70% (95% CI, 40%-93%) in the autologous group. NRM at 3 years was 40% (95% CI, 23%-59%) in the allogeneic group and 11% (95% CI, 0-36%) in the autologous group. Autologous SCT is a safe and feasible treatment option for patients with WM, especially for those who present with adverse prognostic factors. Allogeneic SCT carries a much higher (40%) risk of NRM and should not be considered outside the context of a clinical trial.

Adult↗
PubMed2006

6q deletion discriminates Waldenström macroglobulinemia from IgM monoclonal gammopathy of undetermined significance.

IgM monoclonal gammopathy of undetermined significance (IgM MGUS) and Waldenström macroglobulinemia (WM) are sometimes clinically difficult to distinguish. In our previous study, deletion of the long arm of chromosome 6 (6q) was found in about half of WM patients. To further clarify the area of minimal deletion at 6q (6q-) and to address the issue of whether 6q- occurs in IgM MGUS, 12 IgM MGUS and 38 WM patients were studied by fluorescence in situ hybridization using probes targeting different chromosomal segments of 6q. No 6q deletions were found in IgM MGUS samples. Of 38 successfully studied WM patients, 21 (55%) showed a deletion of 6q. The area of minimal deletion was between 6q23 and 6q24.3, but the deletion usually encompassed a large fragment of the 6q arm. These results indicate that 6q- can distinguish WM from IgM MGUS and is likely to be a secondary event.

Aged↗
PubMed2006

A phase II trial of imatinib in patients with refractory/relapsed myeloma.

Although imatinib was designed to specifically inhibit the bcr-abl gene product, it inhibits other receptor tyrosine kinases including c-kit. As pre-clinical data, 126 patients with plasma cell disorders and 19 controls were evaluated for c-kit expression. Patients were eligible for the treatment trial if they had relapsed/refractory myeloma. The primary end-point of the study was response. Of the 145 studied before the trial, c-kit expression was present on the bone marrow plasma cells of control (11%), AL amyloid (53%), MGUS (47%), SMM (67%) and MM (42%) patients. Twenty-three MM patients were enrolled on the therapeutic trial (imatinib 400 mg daily) and 52% had positive c-kit staining. There were no responses. The median duration of treatment was 48 days (range: 12-349). Patients ended treatment due to progressive disease (18 patients), death (3) and other (2). The data suggest that imatinib is not an active agent in patients with relapsed or refractory multiple myeloma.

Aged↗
PubMed2006

Autologous stem cell transplantation and IgM amyloidosis.

High dose chemotherapy (HDC) followed by autologous stem cell transplant (ASCT) is an accepted form of treatment for patients with AL amyloidosis. The purpose of the current study is to review the outcomes of IgM AL amyloidosis patients treated with high dose chemotherapy and autologous stem cell transplant and compare them to the outcomes of all AL amyloidosis subtypes treated similarly. We retrospectively reviewed the pretransplant characteristics, conditioning regimens and response to transplant of all twelve IgM AL amyloidosis patients who were transplanted at the Mayo Clinic between May 1999 and August 2005. Transplant related mortality was low at 8%. The overall hematologic response rate was 89%. The organ response rate was 67%. Overall median survival has not been reached as eleven patients are still alive. IgM AL amyloidosis patients appear to have similar outcomes after HDC and ASCT as other subtypes of AL amyloidosis suggesting that this therapy is an acceptable form of treatment for patients with IgM amyloidosis, and should be considered as a first line treatment option.

Aged↗
PubMed2006

Natural history of thromboembolism in AL amyloidosis.

To determine the natural history of thromboembolism in patients with biopsy-proven AL amyloidosis, medical records of 2,132 patients evaluated at Mayo Clinic between 1975 and 2000 were reviewed. Forty patients (21 male) were found to have objectively documented thromboembolism. The median age was 65 years. Four patients had a monoclonal gammopathy of undetermined significance, 20 had an unspecified plasma cell proliferative disorder, 11 had multiple myeloma, and 1 had Waldenström macroglobulinemia. Twelve patients had cardiac amyloid, and 20 had renal amyloid. Neither the extent of the amyloid nor the type of monoclonal protein was predictive of the development of thromboembolic events. Thromboembolism preceded the diagnosis of AL amyloidosis in 11 patients, occurred at the time of diagnosis or within 1 month after diagnosis in 11 patients, and occurred 1 month or more after diagnosis in 18 patients. Twenty-nine patients (73%) had venous thrombosis and 11 (28%) had arterial thrombosis. Eight patients (20%) died within 1 month after the thrombotic event, and 18 (45%) died within 1 year. The development of thrombosis in patients with AL amyloidosis appears to predict significant mortality within the first month and year after the event.

Aged↗
PubMed2006

Death during coronary angiography in a woman with cardiac amyloidosis.

Amyloidosis is a well-recognized systemic disease entity. Patients with cardiac amyloidosis have a poor prognosis; the median survival time after development of congestive heart failure is 4 months. We describe a 72-year-old woman with unsuspected cardiac amyloidosis who died during diagnostic coronary angiography. To our knowledge, this is the first report of this complication.

Aged↗