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Taxiarchis V Kourelis,
Morie Gertz,
Clive Zent,
Martha Lacy,
Robert Kyle,
Prashant Kapoor,
Steven Zeldenrust, Francis Buadi,
Thomas Witzig,
Suzanne Hayman,
John Lust,
Stephen Russell,
Yi Lin,
Vincent S Rajkumar,
Shaji Kumar,
Nelson Leung,
David Dingli,
Angela Dispenzieri
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ABSTRACT: To clarify the presentation and course of patients with chronic lymphocytic leukemia (CLL) and amyloidosis. Mayo databases were interrogated for patients who carried a diagnosis of amyloidosis and CLL evaluated at Mayo Clinic, Rochester from January 1974 to October 2012. Charts were abstracted and data analyzed. Of the 33 patients identified, 20 (61%) were diagnosed with AL and 13 (39%) with non-AL. Only four patients had immunoglobulin light chain amyloidosis (AL) that could be solely attributed to the CLL clone; another six had both a plasma cell clone and a CLL clone that shared the same light chain. Median overall survival was 15.6 months for patients with AL and 58.1 months for patients with non-AL. For patients with AL management involved chemotherapy targeted toward monoclonal plasma cells, lymphocytes or both, and for patients with non-AL no specific amyloid treatment was administered. AL is a rare complication of CLL, but in this elderly population of patients non-AL is nearly as common. Distinguishing between these two groups is essential since patients with non-AL amyloidosis have better outcomes and they do not require cytotoxic chemotherapy to treat their amyloidosis. Am. J. Hematol., 2013. © 2013 Wiley Periodicals, Inc.
American Journal of Hematology 02/2013; · 4.67 Impact Factor
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American Journal of Hematology 09/2012; 87(11):E131-2. · 4.67 Impact Factor
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Ivana N M Micallef,
Shirshendu Sinha,
Dennis A Gastineau,
Robert Wolf,
David J Inwards,
Morie A Gertz,
Suzanne R Hayman,
William J Hogan,
Patrick B Johnston,
Martha Q Lacy,
Stephen M Ansell, Francis Buadi,
David Dingli,
Angela Dispenzieri,
Mark R Litzow,
Luis F Porrata,
Jeffrey L Winters,
Shaji Kumar
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ABSTRACT: Historically, up to 30% of patients were unable to collect adequate numbers of peripheral blood stem cells (PBSCs) for autologous stem cell transplantation (ASCT). Plerixafor in combination with granulocyte colony-stimulating factor (G-CSF) has shown superior results in mobilizing peripheral blood (PB) CD34+ cells in comparison to G-CSF alone, but its high cost limits general use. We developed and evaluated risk-adapted algorithms for optimal utilization of plerixafor. In plerixafor-1, PBSC mobilization was commenced with G-CSF alone, and if PB CD34 on day 4 or day 5 was <10/μL, plerixafor was administered in the evening, and apheresis commenced the next day. In addition, if on any day, the daily yield was <0.5 × 10(6) CD34/kg, plerixafor was added. Subsequently, the algorithm was revised (plerixafor-2) with lower thresholds. If day-4 PB CD34 <10/μL for single or <20/μL for multiple transplantations, or day-1 yield was <1.5 × 10(6) CD34/kg, or any subsequent daily yield was <0.5 × 10(6) CD34/kg, plerixafor was added. Three time periods were analyzed for results and associated costs: January to December 2008 (baseline cohort; 319 mobilization attempts in 278 patients); February to November 2009 (plerixafor-1; 221 mobilization attempts in 216 patients); and December 2009 to June 2010 (plerixafor-2; 100 mobilization attempts in 98 patients). Plerixafor-2 shows a significant improvement in PB CD34 collection, increased number of patients reaching minimum and optimal goals, fewer days of apheresis, and fewer days of mobilization/collection, albeit at increased costs. In conclusion, although the earlier identification of ineffective PBSC mobilization and initiation of plerixafor (plerixafor-2) increases the per-patient costs of PBSC mobilization, failure rates, days of apheresis, and total days of mobilization/collection are lower.
Biology of blood and marrow transplantation: journal of the American Society for Blood and Marrow Transplantation 08/2012; · 3.15 Impact Factor
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Jonathan S Bleeker,
Morie A Gertz,
Patricia A Pellikka,
Dirk R Larson, Francis Buadi,
David Dingli,
Angela Dispenzieri,
Suzanne R Hayman,
William Hogan,
Shaji Kumar,
S Vincent Rajkumar,
Martha Q Lacy
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ABSTRACT: Cardiac complications following hematopoietic stem cell transplantation (HSCT) are emerging as a significant concern given the increasing utilization of HSCT for a variety of hematologic malignancies.
We utilized an existing database to determine the frequency of cardiac dysfunction (CD), namely a decrease in left ventricular ejection fraction, following conditioning with high-dose melphalan (HDM) and autologous HSCT for multiple myeloma (MM) and systemic amyloidosis (AL). We then performed a case-control study to examine variables associated with increased risk of CD in this population.
In MM patients undergoing HSCT, the rate of CD was 1.6% (17/1050, 95% CI: [0.9, 2.6]). None of the examined pre-HSCT variables or HDM dose were significantly associated with development of CD in this population. In patients with AL, the rate of CD was 5.6% (24/426, 95% CI: [3.6, 8.3]). On univariate analysis, decision to administer an HDM dose <200 mg/m(2) [odds ratio (OR): 4.59 (1.27-16.57) P = 0.02], pretransplant left ventricular ejection fraction <60% [OR: 17.78 (2.29-138.33) P = 0.006], and documented amyloid involvement of ≥ 3 organs [OR: 4.0 (1.03-15.6) P = 0.046] were associated with the development of CD in the AL population. No other examined peri-transplant factors were associated with development of CD.
To our knowledge, this is the first series to report a significant rate of CD following HDM conditioning and autologous HSCT in patients with AL.
European Journal Of Haematology 06/2012; 89(3):228-35. · 2.61 Impact Factor
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Anita D'Souza,
Martha Lacy,
Morie Gertz,
Shaji Kumar, Francis Buadi,
Suzanne Hayman,
David Dingli,
Steven Zeldenrust,
Robert Kyle,
Stephen Ansell,
David Inwards,
Patrick Johnston,
Ivana Micallef,
Luis Porrata,
Mark Litzow,
Dennis Gastineau,
William Hogan,
Angela Dispenzieri
[show abstract]
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ABSTRACT: The POEMS syndrome (polyradiculoneuropathy, organomegaly, multiple endocrinopathies, monoclonal protein, skin changes) is a rare disease associated with a plasma cell dyscrasia. Patients with disseminated POEMS can be treated with high-dose therapy and autologous stem cell transplantation (ASCT). While clinical improvement is nearly universal in these patients, the long-term outcomes after transplantation are unclear. We therefore assessed the long-term clinical outcomes of 59 POEMS patients treated with ASCT at our institution. With a median follow-up of 45 months, 14 patients have progressed with a progression-free survival of 98% and 75% at 1 and 5 years, respectively. Factors associated with progression have included an IgG-λ monoclonal component (hazard ratio [HR] 7.5; 95% confidence interval [CI], 2.3-28.3; P = .0008), fluorodeoxyglucose-avid lesions on baseline positron emission tomography (HR 6.4; 95% CI, 1.2-120; P = .03), lack of complete hematologic response (HR 5.4; 95% CI, 1.8-16.7; P = .003), and patients aged 50 years or younger at transplantation (HR 4.4; 95% CI, 1.3-20; P = .01). The most common progression events have been radiologic followed by rising VEGF. Symptomatic progression has been rare. Most patients could be salvaged with immunomodulatory drugs or radiation. The 5-year survival is 94%. Herein, we describe a system of monitoring response and progression among patients with POEMS after ASCT.
Blood 05/2012; 120(1):56-62. · 9.90 Impact Factor
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ABSTRACT: Immunoglobulin light chain (AL) amyloidosis is the most common acquired systemic amyloidoses. Its presentation is often insidious and progressive, which may delay diagnosis. The interval between first symptoms and actual diagnosis along the intrinsic heterogeneity of tissue tropism create a wide spectrum of presentations, both in terms of scope and depth of symptoms and signs and functional status of patients. In this review, the authors review the pathogenesis, diagnosis and differential diagnosis of AL amyloidosis along with the prognosis and state-of-the-art management for patients with this affliction.
Blood reviews 04/2012; 26(4):137-54. · 7.19 Impact Factor
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Angela Dispenzieri, Francis Buadi,
Kristina Laumann,
Betsy LaPlant,
Suzanne R Hayman,
Shaji K Kumar,
David Dingli,
Steven R Zeldenrust,
Joseph R Mikhael,
Robert Hall, [......],
Craig Reeder,
Rafael Fonseca,
P Lief Bergsagel,
A Keith Stewart,
Vivek Roy,
Thomas E Witzig,
John A Lust,
Stephen J Russell,
Morie A Gertz,
Martha Q Lacy
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[hide abstract]
ABSTRACT: Immunoglobulin light-chain (AL) amyloidosis is a rare, incurable plasma cell disorder. Its therapy has benefited immensely from the expanding drug armamentarium available for multiple myeloma. Pomalidomide in combination with weekly dexamethasone (Pom/dex) is active among patients with relapsed myeloma. In the present study, we explored the Pom/dex combination in patients with previously treated AL. Patients were eligible for this prospective phase 2 trial if they had had at least one prior regimen and if they had reasonably preserved organ function. Patients were treated with oral Pom/dex. Thirty-three patients were enrolled. The median age was 66 years. Median time from diagnosis to on-study was 37 months. Eighty-two percent had cardiac involvement. The confirmed hematologic response rate was 48%, with a median time to response of 1.9 months. Organ improvement was documented in 5 patients. The median overall and progression-free survival rates were 28 and 14 months, respectively; the 1-year overall and progression-free survival rates were 76% and 59%, respectively. There was a discordance between the hematologic response and the N-terminal pro-brain natriuretic peptide response. The most common grade 3-5 adverse events, regardless of attribution, were neutropenia and fatigue. We conclude that pomalidomide appears to be a valuable drug covering an unmet clinical need in patients with previously treated AL. The trial is registered at www.clinicaltrials.gov as NCT00558896.
Blood 04/2012; 119(23):5397-404. · 9.90 Impact Factor
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Rahma Warsame,
Morie A Gertz,
Martha Q Lacy,
Robert A Kyle, Francis Buadi,
David Dingli,
Philip R Greipp,
Suzanne R Hayman,
Shaji K Kumar,
John A Lust,
Stephen J Russell,
Thomas E Witzig,
Joseph Mikhael,
Nelson Leung,
Steven R Zeldenrust,
S Vincent Rajkumar,
Angela Dispenzieri
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ABSTRACT: Over the years, the definition of solitary plasmacytoma of bone (SPB) has shifted in part due to more modern testing capabilities. We hypothesized that outcomes data based on antiquated testing would not reflect outcomes using modern staging. To address both how widely applied adequate diagnostic staging is and what the progression rates of SPB as defined with state-of-the-art staging are, we performed a retrospective chart review of those patients with a diagnosis of SPB seen at our institution over the past decade. Two groups were studied: all patients with SPB (n = 127); and those patients referred to our institution for an indication other than progression (n = 91). The median PFS for those two groups were 26 months and 42 months, respectively. At baseline, only a minority of patients had state-of-the-art staging. The 5 patients with both modern imaging and a negative bone marrow had a 21 month PFS of 100%. Patients with plasmacytoma plus, one plasmacytoma but bone marrow consistent with monoclonal gammopathy of undetermined significance, fare worse than true SPB. The use of modern testing is imperative to characterize a patient's risk for progression. PET/CT plays an important role in the diagnostic work-up.
American Journal of Hematology 03/2012; 87(7):647-51. · 4.67 Impact Factor
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Anita D'Souza,
Suzanne R Hayman, Francis Buadi,
Michelle Mauermann,
Martha Q Lacy,
Morie A Gertz,
Robert A Kyle,
Shaji Kumar,
Philip R Greipp,
John A Lust,
Stephen J Russell,
Steven Zeldenrust,
David Dingli,
Thomas E Witzig,
S Vincent Rajkumar,
Angela Dispenzieri
[show abstract]
[hide abstract]
ABSTRACT: The POEMS syndrome is associated with elevated vascular endothelial growth factor (VEGF) levels. Several studies have compared serum VEGF levels between POEMS patients and other disease entities showing higher serum VEGF in POEMS syndrome; however, it is unknown whether serum levels are reliable and reproducible given variable platelet release of VEGF. We therefore compared plasma levels of VEGF in 29 patients with POEMS syndrome with those of other disorders (n = 76). We demonstrated that plasma VEGF levels are useful in differentiating POEMS from other plasma cell dyscrasias, neuropathic processes, and multisystem illnesses. Plasma VEGF is also useful in monitoring disease activity after treatment and correlates with clinical improvements better than hematologic response.
Blood 08/2011; 118(17):4663-5. · 9.90 Impact Factor
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Francis Buadi,
Ann W Hsing,
Jerry A Katzmann,
Ruth M Pfeiffer,
Adam Waxman,
Edward D Yeboah,
Richard B Biritwum,
Yao Tettey,
Andrew Adjei,
Lisa W Chu,
Angelo DeMarzo,
George J Netto,
Angela Dispenzieri,
Robert A Kyle,
S Vincent Rajkumar,
Ola Landgren
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ABSTRACT: Chronic antigenic stimulation is associated with hypergamma-globulinemia. Higher rates of hypergamma-globulinemia in tropical populations are maintained even with migration to temperate regions. We conducted a population-based screening study to assess the prevalence and risk factors for hypergamma-globulinemia in Ghana, Africa. 917 Ghanaian males (50-74 years) underwent in-person interviews and health examinations. Serum from all persons was analyzed by electrophoresis performed on agarose gel; serum with a discrete/localized band was subjected to immunofixation. 54 persons with monoclonal proteins were excluded and 17 samples were insufficient for analysis. Using logistic regression and Chi-square statistics we analyzed patterns of hypergamma-globulinemia. Among 846 study subjects, the median γ-globulin level was 1.86 g/dL. On the basis of a U.S. reference, 616 (73%) had hypergamma-globulinemia (>1.6 g/dL) and 178 (21%) had γ-globulin levels >2.17 gm/dl. On multivariate analyses, lower education status (P = 0.0013) and never smoking (P = 0.038) were associated with increased γ-globulin levels. Self-reported history of syphilis was associated with hypergamma-globulinemia. We conclude that three quarters of this population-based adult Ghanaian male sample had hypergamma-globulinemia with γ-globulin levels >1.6 g/dL. Future studies are needed to uncover genetic and environmental underpinnings of our finding, and to define the relationship between hypergamma-globulinemia, monoclonal gammopathy of undetermined significance (MGUS), and multiple myeloma.
American Journal of Hematology 07/2011; 86(7):554-8. · 4.67 Impact Factor
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Martha Q Lacy,
Jacob B Allred,
Morie A Gertz,
Suzanne R Hayman,
Kristen Detweiler Short, Francis Buadi,
Angela Dispenzieri,
Shaji Kumar,
Philip R Greipp,
John A Lust, [......],
Steven Zeldenrust,
Rafael Fonseca,
P Leif Bergsagel,
Vivek Roy,
A Keith Stewart,
Kristina Laumann,
Sumithra J Mandrekar,
Craig Reeder,
S Vincent Rajkumar,
Joseph R Mikhael
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ABSTRACT: Pomalidomide at doses of 2 or 4 mg/d has demonstrated excellent activity in patients with multiple myeloma (MM). We opened 2 sequential phase 2 trials using the pomalidomide with weekly dexamethasone (Pom/dex) regimen at differing doses to study the efficacy of this regimen in patients who have failed both lenalidomide and bortezomib. Pomalidomide was given orally 2 or 4 mg daily with dexamethasone 40 mg weekly. Thirty-five patients were enrolled in each cohort. Confirmed responses in the 2-mg cohort consisted of very good partial response (VGPR) in 5 (14%), partial response (PR) in 4 (11%), minor response (MR) in 8 (23%) for an overall response rate of 49%. In the 4-mg cohort, confirmed responses consisted of complete response (CR) in 1 (3%), VGPR in 3 (9%), PR in 6 (17%), MR in 5 (14%) for an overall response rate of 43%. Overall survival at 6 months is 78% and 67% in the 2- and 4-mg cohort, respectively. Myelosuppression was the most common toxicity. This nonrandomized data suggests no advantage for 4 mg over the 2 mg daily. Pomalidomide overcomes resistance in myeloma refractory to both lenalidomide and bortezomib. This trial is registered at http://ClinicalTrials.gov, number NCT00558896.
Blood 06/2011; 118(11):2970-5. · 9.90 Impact Factor
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Sumit Madan,
Martha Q Lacy,
Angela Dispenzieri,
Morie A Gertz, Francis Buadi,
Suzanne R Hayman,
Kristen Detweiler-Short,
David Dingli,
Steven Zeldenrust,
John Lust,
Philip R Greipp,
S Vincent Rajkumar,
Shaji Kumar
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ABSTRACT: The efficacy of retreatment with immunomodulatory drugs (IMiDs) among patients with multiple myeloma who received this class of drugs for initial therapy is unknown. We studied 140 patients who received either thalidomide-dexamethasone (81; 58%) or lenalidomide-dexamethasone (59; 42%) as first-line therapy of multiple myeloma followed by repeat IMiD (thalidomide [34; 24%] or lenalidomide [106; 76%]) as one of the salvage regimens. A median of 2 treatments (range, 1-6), including a stem cell transplant in 105 patients (75%), were administered before IMiD-based salvage therapy. The median time from diagnosis to repeat exposure to IMiD was 28 months. Among the 113 evaluable patients, 50 (44%) achieved at least a partial response, and 63 (56%) achieved less than a partial response to repeat IMiD. Response rates with lenalidomide retreatment were higher than with repeat administration of thalidomide.
Blood 06/2011; 118(7):1763-5. · 9.90 Impact Factor
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[show abstract]
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ABSTRACT: Monoclonal gammopathy of undetermined significance (MGUS) is defined as a serum M protein level of less than 3 g/dL, less than 10% clonal plasma cells in the bone marrow, and the absence of end-organ damage. The prevalence of MGUS is 3.2% in the white population but is approximately twice that high in the black population. MGUS may progress to multiple myeloma, AL amyloidosis, Waldenström macroglobulinemia, or lymphoma. The risk of progression is approximately 1% per year, but the risk continues even after more than 25 years of observation. Risk factors for progression include the size of the serum M protein, the type of serum M protein, the number of plasma cells in the bone marrow, and the serum free light chain ratio. Smoldering (asymptomatic) multiple myeloma (SMM) is characterized by the presence of an M protein level of 3 g/dL or higher and/or 10% or more monoclonal plasma cells in the bone marrow but no evidence of end-organ damage. The overall risk of progression to a malignant condition is 10% per year for the first 5 years, approximately 3% per year for the next 5 years, and 1% to 2% per year for the following 10 years. Patients with both MGUS and SMM must be followed up for their lifetime.
Oncology (Williston Park, N.Y.) 06/2011; 25(7):578-86. · 1.03 Impact Factor
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Sergio Siragusa,
William Morice,
Morie A Gertz,
Robert A Kyle,
Philip R Greipp,
John A Lust,
Thomas E Witzig,
Martha Q Lacy,
Steven R Zeldenrust,
S Vincent Rajkumar,
Stephen J Russell,
Suzanne R Hayman, Francis Buadi,
Shaji K Kumar,
David Dingli,
Angela Dispenzieri
[show abstract]
[hide abstract]
ABSTRACT: The rate of asymptomatic amyloidosis (AL) among patients with newly diagnosed multiple myeloma (MM) or smoldering multiple myeloma (SMM) is unknown. We evaluated number and clinical significance of asymptomatic AL in consecutive MM and SMM patients, not having recognition of symptomatic AL at the time of their diagnostic bone marrow biopsy. Bone marrow biopsies were stained with Congo red and considered diagnostic for AL in case of positive Congo red staining with apple-green birefringence. Biopsies from 144 patients were evaluated: 77 had a diagnosis of MM and 67 of SMM. The median age was 59 (range 26-84) years; the median follow-up was 76 months (range 0-216). Immunoglobulin isotypes were 96/144 (67%), IgG; 23/144 (16%), IgA; 12/144 (8%), light chain only; 1/77 (1%), IgD; and biclonal or indeterminate, 12/144 (8%). Fifty-eight percent (84/144) were κ restricted. The presence of amyloid was found in two cases (1%, 95% CI -0.6 to 3.2), one in MM, and one in SMM group, and none had or developed signs or symptoms suggestive of organ involvement by amyloid. Among the 142 other patients without amyloid deposition in their index bone marrow, one (0.7%, 95% CI -0.6 to 2.0) developed symptomatic AL after 119 months.
Annals of Hematology 01/2011; 90(1):101-6. · 2.62 Impact Factor
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[show abstract]
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ABSTRACT: All patients with proven light chain amyloidosis deserve a trial of therapy. Although high dose therapy has been shown to
be highly effective, only a quarter of patients are actually eligible for this technique. Lower intensity treatments are required
for the majority of patients. We review the history of treatment of amyloidosis beginning with the use of conventional alkylating
agent chemotherapy, the role of the novel agents bortezomib, lenalidomide, and thalidomide in the treatment of amyloidosis.
A suggested treatment algorithm is given to help guide decisions regarding therapy.
KeywordsMelphalan-Dexamethasone-Chemotherapy-Treatment of amyloidosis-Thalidomide-Lenalidomide-Bortezomib
06/2010: pages 155-164;
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Prashant Kapoor,
Rafael Fonseca,
S Vincent Rajkumar,
Shirshendu Sinha,
Morie A Gertz,
A Keith Stewart,
P Leif Bergsagel,
Martha Q Lacy,
David D Dingli,
Rhett P Ketterling, Francis Buadi,
Robert A Kyle,
Thomas E Witzig,
Philip R Greipp,
Angela Dispenzieri,
Shaji Kumar
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[hide abstract]
ABSTRACT: Overall survival (OS) has improved with increasing use of novel agents in multiple myeloma (MM). However, the disease course remains highly variable, and the heterogeneity largely reflects different genetic abnormalities. We studied the impact of the Mayo risk-stratification model of MM on patient outcome in the era of novel therapies, evaluating each individual component of the model-fluorescence in situ hybridization (FISH), conventional cytogenetics (CG), and the plasma cell labeling index-that segregates patients into high- and standard-risk categories. This report consists of 290 patients with newly diagnosed MM, predominantly treated with novel agents, who were risk-stratified at diagnosis and were followed up for OS. Of these patients, 81% had received primarily thalidomide (n=50), lenalidomide (n=199), or bortezomib (n=79) as frontline or salvage therapies. Our retrospective analysis validates the currently proposed Mayo risk-stratification model (median OS, 37 months vs not reached for high- and standard-risk patients, respectively; P=.003). Although the FISH or CG test identifies a high-risk cohort with hazard ratios of 2.1 (P=.006) and 2.5 (P=.006), respectively, the plasma cell labeling index cutoff of 3% fails to independently prognosticate patient risk (hazard ratio, 1.4; P=.41). In those stratified as standard-risk by one of the 2 tests (FISH or CG), the other test appears to be of additional prognostic significance. This study validates the high-risk features defined by FISH and CG in the Mayo risk-stratification model for patients with MM predominantly treated with novel therapies based on immunomodulatory agents.
Mayo Clinic Proceedings 06/2010; 85(6):532-7. · 5.70 Impact Factor
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Trista Stankowski-Drengler,
Morie A Gertz,
Jerry A Katzmann,
Martha Q Lacy,
Shaji Kumar,
Nelson Leung,
Suzanne R Hayman, Francis Buadi,
Robert A Kyle,
S Vincent Rajkumar,
Angela Dispenzieri
[show abstract]
[hide abstract]
ABSTRACT: POEMS (polyneuropathy, organomegaly, endocrinopathy, monoclonal gammopathy, skin changes) syndrome is a rare paraneoplastic syndrome in which nearly all patients have a monoclonal lambda restricted plasma cell disorder. We investigated whether patients with POEMS have abnormal serum immunoglobulin free light chain (FLC) ratios. Fifty patients with newly diagnosed POEMS syndrome were assessed. Cystatin C levels were measured to discern whether subclinical renal insufficiency could account for FLC elevations in the presence of a normal FLC ratio. Forty-five patients (90%) had elevated lambda FLC; however, only nine (18%) had abnormal FLC ratios. The rise in serum FLC of POEMS patients appeared to be multifactorial-both a function of subclinical renal insufficiency and polyclonal activation of medullary and extramedullary plasma cells. Those patients expressing a clonal IgA were more likely to have clonal plasmacytosis observed on iliac crest biopsy than those with IgG. In summary, serum immunoglobulin profiles are unique in POEMS syndrome as compared with other plasma cell disorders.
American Journal of Hematology 06/2010; 85(6):431-4. · 4.67 Impact Factor
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Angela Dispenzieri,
Gregory A Wiseman,
Martha Q Lacy,
Suzanne R Hayman,
Shaji K Kumar, Francis Buadi,
David Dingli,
Krista M Laumann,
Jake Allred,
Susan M Geyer,
Mark R Litzow,
Dennis A Gastineau,
David J Inwards,
Ivana N Micallef,
Stephen M Ansell,
Luis Porrata,
Michelle A Elliott,
Patrick B Johnston,
William J Hogan,
Morie A Gertz
[show abstract]
[hide abstract]
ABSTRACT: Multiple myeloma (MM) remains an incurable illness affecting nearly 20,000 individuals in the United States per year. High-dose melphalan (HDM) with autologous hematopoietic stem cell support (ASCT) is one of the mainstays of therapy for younger patients, but little advancement has been made with regards to conditioning regimens. We opted to combine (153)Samarium ethylenediaminetetramethylenephosphonate ((153)Sm-EDTMP), a radiopharmaceutical approved for the palliation of pain caused by metastatic bone lesions, with HDM and ASCT in a Phase II study. Individualized doses of (153)Sm were based on dosimetry and were calculated to deliver 40 Gy to the bone marrow. The therapeutic dose of (153)Sm-EDTMP was followed by HDM and ASCT. Forty-six patients with newly diagnosed or relapsed disease were treated. Study patients were compared to 102 patients contemporaneously treated with HDM and ASCT. Fifty-nine percent of study patients achieved a very good partial response (VGPR) or better. With a median follow-up of 7.1 years, the median overall survival and progression free survival (PFS) from study registration was 6.2 years (95% CI 4.6-7.5 years) and 1.5 years (1.1-2.2 years), respectively, which compared favorably to contemporaneously treated non-study patients. Addition of high-dose (153)Sm-EDTMP to melphalan conditioning appears to be safe, well tolerated, and worthy of further study in the context of novel agents and in the Phase III setting.
American Journal of Hematology 06/2010; 85(6):409-13. · 4.67 Impact Factor
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[show abstract]
[hide abstract]
ABSTRACT: To identify and assess the clinical features and treatment response of light chain (AL) amyloidosis diagnosed in patients with previous diagnosis of multiple myeloma (MM).
From a prospectively maintained database, we identified 47 patients seen between January 1, 1990, and August 31, 2008, with a diagnosis of AL amyloidosis that was made at least 6 months after MM diagnosis; these patients form the study group.
Among the 47 patients, 36 developed typical features, 3 had atypical features, and 8 had an incidental finding of amyloidosis. Amyloid deposits were demonstrated in bone marrow, subcutaneous fat aspirate, or organ biopsy in 24, 19, and 12 patients, respectively. One organ was involved in 29 patients (62%), whereas 11 patients (23%) had involvement in more than one organ. At diagnosis of AL amyloidosis, treatment was changed or started in 22 patients, whereas the same treatment was continued in 21 patients, and no treatment data were available for the rest. The best hematologic response included partial response or better in 11 patients (23%) and stable disease in 18 patients (38%). Improvement in an organ was seen in 3 of the 21 evaluable patients. The median overall survival from diagnosis of AL amyloidosis was 9.1 months (95% confidence interval, 4-14). Of the 6 patients still alive, 2 underwent peripheral blood stem cell transplant, and none had cardiac involvement or involvement in more than one organ.
Delayed onset of AL amyloidosis is rarely seen in patients with MM and requires a high index of suspicion for prompt diagnosis. Outcome of these patients is poor, especially in the presence of cardiac involvement.
Mayo Clinic Proceedings 03/2010; 85(3):232-8. · 5.70 Impact Factor
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Francesca Gay,
Suzanne R Hayman,
Martha Q Lacy, Francis Buadi,
Morie A Gertz,
Shaji Kumar,
Angela Dispenzieri,
Joseph R Mikhael,
P Leif Bergsagel,
David Dingli, [......],
John A Lust,
Stephen J Russell,
Vivek Roy,
Steven R Zeldenrust,
Thomas E Witzig,
Rafael Fonseca,
Robert A Kyle,
Philip R Greipp,
A Keith Stewart,
S Vincent Rajkumar
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ABSTRACT: The objective of this case-control study was to compare the efficacy and toxicity of lenalidomide plus dexamethasone (len/dex) versus thalidomide plus dexamethasone (thal/dex) as initial therapy for newly diagnosed myeloma. We retrospectively studied 411 newly diagnosed patients treated with len/dex (228) or thal/dex (183) at the Mayo Clinic. The differences were similar in a matched-pair analysis that adjusted for age, sex, transplantation status, and dexamethasone dose. The proportions of patients achieving at least a partial response to len/dex and thal/dex were 80.3% versus 61.2%, respectively (P < .001); very good partial response rates were 34.2% and 12.0%, respectively (P < .001). Patients receiving len/dex had longer time to progression (median, 27.4 vs 17.2 months; P = .019), progression-free survival (median, 26.7 vs 17.1 months; P = .036), and overall survival (median not reached vs 57.2 months; P = .018). A similar proportion of patients in the 2 groups experienced at least one grade 3 or 4 adverse event (57.5% vs 54.6%, P = .568). Main grade 3 or 4 toxicities of len/dex were hematologic, mainly neutropenia (14.6% vs 0.6%, P < .001); the most common toxicities in thal/dex were venous thromboembolism (15.3% vs 9.2%, P = .058) and peripheral neuropathy (10.4% vs 0.9%, P < .001). Len/dex appears well-tolerated and more effective than thal/dex. Randomized trials are needed to confirm these results.
Blood 12/2009; 115(7):1343-50. · 9.90 Impact Factor
