The Incidence of Atrial Fibrillation Among Patients with AL Amyloidosis Undergoing High Dose Melphalan and Stem Cell Transplantation (HDM/SCT): Experience at a Single Institution

Blood ◽  
2015 ◽  
Vol 126 (23) ◽  
pp. 5490-5490 ◽  
Author(s):  
Dina Brauneis ◽  
Monica Arun ◽  
Frederick L Ruberg ◽  
Anthony C Shelton ◽  
John Mark Sloan ◽  
...  
Keyword(s):  
Atrial Fibrillation ◽  
Stem Cell ◽  
Patient Characteristics ◽  
Ventricular Rate ◽  
High Dose ◽  
Al Amyloidosis ◽  
Hemodynamic Stability ◽  
Atrial Size ◽  
History Of ◽  
High Dose Melphalan

Abstract Background High dose melphalan and autologous stem cell transplantation (HDM/SCT) can induce hematologic responses and prolong survival in selected patients with AL amyloidosis. However, cardiac toxicity associated with HDM/SCT remains an ongoing concern in patients with AL amyloidosis. Atrial fibrillation (AF) may complicate SCT 4-10% of the time (Olivieri et al. 1998, Hidalgo et al. 2004). The development of AF in the SCT period can be challenging to manage. Studies identifying risk factors for the development of AF in amyloidosis are limited (Abhishek et al. 2013). Objective We sought to determine the incidence of atrial fibrillation in patients with AL amyloidosis undergoing SCT. Patients and methods We retrospectively analyzed charts of 91 consecutive patients undergoing HDM/SCT for AL amyloidosis between January 2011 and May 2015. The peri-transplant period was defined from the first day of stem cell mobilization until the time to engraftment. For all patients, medical records were reviewed for age, gender, prior history of AF, baseline troponin I, brain natriuretic peptide (BNP), baseline echocardiography, dose of Melphalan, ventricular rate at the time of AF event, hemodynamic stability (based on blood pressure), AF management and the return to normal sinus rhythm (NSR). Results Ninety-one patients with AL Amyloidosis underwent HDM/SCT from January 2011 to May 2015. Overall, twelve patients (13.1%) developed AF during SCT period, at a median of D+9 (range, D-10 to D+21). Baseline characteristics of these patients are listed in Table 1. Patient characteristics and AF management are listed in Table 2. Of note, there were three patients who had a history of PAF who did not develop AF during the peri-transplant period. Conclusion AF occurred in 13.1% of patients with AL amyloidosis undergoing HDM/SCT in the peri-transplant period, a rate higher than previously reported in other patient populations. Four of seven patients with a history of supraventricular tachyarrhythmia (SVT) developed AF during the peri-transplant period, making prior SVT a potential risk factor. The presence of cardiac amyloidosis, even in early stages, in combination with high dose Melphalan, may also predispose this group of patients to supraventricular arrhythmias. The identification of risk factors for developing AF in patients with AL amyloidosis may enable the use of preventative action in the future. Table 1. Patient Characteristics at Baseline N = 12 (%) Median Age, years (range) 59.5 (40-68) Gender Male Female 6 (50) 6 (50) Organ Involvement Cardiac only Renal only Pulmonary only Cardiac and renal 3 (25.0) 4 (33.3) 1 (8.3) 4 (33.3) History of AfibPrior anticoagulation Prior rate control 4 (33.3) 2/4 (50.0) 4/4 (100.0) Median BNP, pg/mL (range) 59.5 (17-558) Median Troponin, ng/mL (range) 0.0385 (0.006 - 0.446) Median TSH*, IU/mL (range) 1.56 ( 0.24-5.39) Cardiac Echo IVSD**, mm (range) Presence of diastolic dysfunction Diastolic Dysfunction, grade (range) LVEF***, % (range) Left atrial size****, mm (range) 11.5 ( 8.0-17.0)8 (66.6) 1.0 ( 0.0-3.0)61.6 ( 44-71)36.5 ( 23-43) Median PR interval on EKG in ms, (range) 183 (132-230) Dose of Melphalan140mg/m2 200mg/m2 4(33.3) 8(66.6) *TSH: Thyroid stimulating hormone **IVSD: Interventricular septal diastolic thickness (normal < 10mm for women and < 11mm for men) ***LVEF: Left ventricular ejection fraction **** Left atrial size in parasternal long axis view (normal < 40mm) Table 2. Patient Characteristics at Time of AF Event N = 12 (%) Median Day to event as it relates to stem cell infusion, (range) D+9 (D-10 to D+21) Median Ventricular Rate, beats per minute (range) 130 (83-159) Hemodynamic Stability Stable Unstable 5(41.6) 7(58.3) Treatment of rate/rhythm Beta blocker alone Calcium channel blocker Amiodarone and beta blocker No specific intervention 5(41.7) 0 (0.0) 3(33.3) 4(33.3) Anticoagulation Yes No 3(33.3) 9(75.0) Disclosures No relevant conflicts of interest to declare.

Induction Therapy with Bortezomib and Dexamethasone Followed By Autologous Stem Cell Transplantation for Systemic Light Chain Amyloidosis: Our Experience

Blood ◽  
2014 ◽  
Vol 124 (21) ◽  
pp. 5907-5907
Author(s):  
Sandeep Jain ◽  
Luciano J Costa ◽  
Robert K Stuart ◽  
Saurabh Chhabra ◽  
Alice Mims ◽  
...  
Keyword(s):  
Stem Cell ◽  
Cardiac Involvement ◽  
Stem Cell Transplant ◽  
Patient Characteristics ◽  
Autologous Stem Cell Transplant ◽  
High Dose ◽  
Al Amyloidosis ◽  
Cell Transplant ◽  
High Dose Melphalan

Abstract Introduction: The optimal treatment approach for systemic AL amyloidosis remains unclear. Autologous stem cell transplant (ASCT) is the only modality associated with long term survival, but failure to show survival benefit in randomized clinical trial raises doubts about its efficacy 1, 2. Outcomes after ASCT are better in patients who achieve complete hematologic response after the ASCT3. One report has shown improved outcomes with combining one dose of the proteasome inhibitor bortezomib with high dose melphalan as part of conditioning regimen 4. Preliminary data from a recent study suggest that the outcome of treating AL amyloidosis with two cycles of bortezomib and dexamethasone followed by ASCT was superior to the outcome of the ASCT alone5. We describe our experience with giving 4-6 cycles of bortezomib and dexamethasone induction prior to high dose melphalan and ASCT in patients with systemic AL amyloidosis. Patients and methods: We included all patients who underwent autologous transplant for symptomatic systemic AL amyloidosis at our institution from October 2010 till June 2014. Five patients were included in the analysis and patient characteristics are described in table 1. All patient received 4 -6 cycles of induction with bortezomib and dexamethasone followed by autologous stem cell transplant using high dose melphalan (200 mg/m2). One patient also received six cycles of lenalidomide and dexamethasone prior to bortezomib based induction for lack of response. Hematologic and organ response were assessed using the definitions from the 10th International symposium on Amyloid and Amyloidosis. Overall survival was calculated by Kaplan Meyer’s method using Graphpad Prism 6.0 software. Results: There was no transplant related mortality. After median follow up of 13 months (12-25 months) all patient are alive. Toxicities from the ASCT were mostly cytopenias in the immediate post-transplant period which were managed as per the standard of care. Two patients achieved hematological complete response while one more had very good partial response and other two achieved partial response. Of the four patients with nephrotic range proteinuria, two patients had > 95% reduction in proteinuria, one had > 75% reduction in proteinuria and another patient had > 50% reduction in proteinuria. One patient had Liver involvement with elevated alkaline phosphatase which normalized post-transplant (table 2). The responses were maintained on last follow up and none of the patient had hematological or organ relapses. Discussion: Bortezomib alone and in combination with steroids has shown efficacy in AL amyloidosis, but its role in induction prior to high dose melphalan/ASCT to help achieve deeper hematological response is unknown. Our experience shows that this combination may be highly efficacious without significant toxicity. Limitations of our study include the small number of patients and absence of any patients with cardiac involvement, which is a worse prognostic marker. We conclude that the bortezomib and dexamethasone induction followed by high dose melphalan/ASCT for AL amyloidosis should be studied in prospective trials. Table 1.Patient Characteristics n=5Age, years 51.2 (44-62)Race (Caucasian)4 (80%)Gender ( female)3 (60%)Cardiac involvement 0 (0)Renal involvement 4 (80%)Serum creatinine ≥ 2.5 0 (0)Organ involvement ≥21 (20%)BM plasma cells > 10%1 (20%)Hgb ≤ 10 g/dl0 (0)LVEF <50%0 (0)Induction therapy Bortezomib/dexamethasone only4 (80%)Lenalidomide/dexamethasone + Bortezomib/dexamethasone1 (20%) Table 2. Outcomes n=5 Baseline After ASCT Hematologic response n=5 M protein 0.772 gm/dl 0.096 gm/dl 2 CR, 1 VGPR, 2 PR Renal response n=4 24 hours proteinuria 3.13 gm 0.432 gm 2 > 95% reduction, 1 >75% reduction, 1 >50 % reduction. Liver response n=1 Alkaline phosphatase 700 IU/L 62 IU/L Disclosures No relevant conflicts of interest to declare.

Short and long-term outcome of treatment with high-dose melphalan and stem cell transplantation for multiple myeloma-associated AL amyloidosis

2009 ◽  
Vol 89 (6) ◽  
pp. 579-584 ◽  
Author(s):  
Saulius Girnius ◽  
David C. Seldin ◽  
Martha Skinner ◽  
Kathleen T. Finn ◽  
Karen Quillen ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Stem Cell ◽  
Stem Cell Transplantation ◽  
High Dose ◽  
Al Amyloidosis ◽  
Term Outcome ◽  
Long Term Outcome ◽  
Short And Long Term ◽  
High Dose Melphalan

Second Autologous Peripheral Blood Stem Cell Transplantation with High Dose Melphalan (HDM/SCT) in Patients Relapsing After An Initial Course of HDM/SCT for the Treatment of AL Amyloidosis.

Blood ◽  
2009 ◽  
Vol 114 (22) ◽  
pp. 2318-2318
Author(s):  
Karen Quillen ◽  
David C. Seldin ◽  
Kathleen T. Finn ◽  
Vaishali Sanchorawala
Keyword(s):  
Stem Cell ◽  
Conflicts Of Interest ◽  
Plasma Cell Dyscrasia ◽  
High Dose ◽  
Time Interval ◽  
Al Amyloidosis ◽  
Clinical Relapse ◽  
Cell Transplant ◽  
Organ Function ◽  
High Dose Melphalan

Abstract Abstract 2318 Poster Board II-295 High-dose melphalan and autologous stem cell transplant (HDM/SCT) can induce complete hematologic responses (CR), defined as disappearance of the underlying monoclonal gammopathy from serum and urine by immunofixation electrophoresis, and of the clonal plasma cell dyscrasia by bone marrow immunohistochemistry, and extend survival in patients with AL amyloidosis. HDM/SCT results in a CR in 40% of patients, and leads to clinical improvements in organ function in >70% of those who achieve a CR. However, hematologic and clinical relapses occur in ∼8% of patients who initially achieve a CR. Tandem cycles of HDM/SCT, which are typically performed within 12 months of each other, have been shown to achieve a higher ultimate CR rate of >60%. Among patients who do not achieve a CR following a single cycle of HDM/SCT, 30% nonetheless experience improvement in organ function. However, in this latter group, clinical improvement is not durable. We designed a study to explore the feasibility, and efficacy, of a second cycle of HDM/SCT in patients who relapse after initially responding to a first cycle of HDM/SCT. Results: Eleven patients, median age 55 (range 39-62), M:F 7:4, who had achieved hematologic and clinical responses after an initial cycle of HDM/SCT, were treated with a second cycle of HDM/SCT when a hematologic and/or clinical relapse occurred after a median time interval of 34 months (range 12-63). Five patients underwent a second course of G-CSF mobilization and a mean of 5.1 million (range 3.4-7.6 million) CD34 cells/kg was collected in a median of 2 days; the other patients had cells saved from the first mobilization. Six patients received 200 mg/m2 HDM; 5 patients received modified high-dose HDM at 140 mg/m2. Engraftment occurred at a median of 10 days for neutrophils, and 12 days for platelets (two days without platelet transfusion support); this engraftment timing is similar to that following the initial transplants (10 days for neutrophils, 13 days for platelets). There was no treatment-related mortality, but toxicity was moderate; almost all patients (except one) experienced grade III/IV non-hematologic toxicities. Of the 11 patients, 3 achieved hematologic CR at one year; these patients are alive and in continuous remission at 2-6 yr after the second transplant, including one patient who received a subsequent renal transplant. Three patients died of progressive disease at 1-2 years after the second transplant. Five patients are alive at 1-3 years post second transplant, in partial remission. Conclusion: 27% (3/11) of patients with AL amyloidosis who experience a hematologic or clinical relapse after responding to initial HDM/SCT can achieve a hematologic CR with a second course of HDM/SCT. Disclosures: No relevant conflicts of interest to declare.

High Dose Melphalan with Autologous Stem Cell Transplantation Overcomes Poor Prognosis of Primary Amyloidosis

Blood ◽  
2010 ◽  
Vol 116 (21) ◽  
pp. 1350-1350
Author(s):  
Simrit Parmar ◽  
Mubeen Khan ◽  
Gabriela Rondon ◽  
Nina Shah ◽  
Qaiser Bashir ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Stem Cell ◽  
Plasma Cells ◽  
High Dose ◽  
Al Amyloidosis ◽  
Hematologic Response ◽  
Bone Marrow Plasma ◽  
Organ Response ◽  
High Dose Melphalan

Abstract Abstract 1350 Background: Systemic Primary AL Amyloidosis is a rare but potentially fatal disease resulting from tissue deposits of amyloid fibrils derived from monoclonal immunoglobulin light chains. High-dose melphalan followed by autologous hematopoietic stem cell transplant (auto HCT) is associated with hematologic and organ responses and improved survival. Methods: In this retrospective analysis we identified 46 patients with primary AL amyloidosis who received auto HCT between 01/1998 to 05/2010 at MDACC. Organ responses were determined using Amyloidosis Consensus Criteria. Results: The median age at auto HSCT was 56 years (34-74) where 61% were males and 35% were older than 60 years of age. 61% had lambda light chain restriction and only 4% had cytogenetic abnormalities. Disease characteristics are summarized in Table 1. The median time from diagnosis to auto HCT was 6.6 months (2.2-29.4 months). 22 pts (47.8%) had one organ, 19 pts (41.3%) had 2 organ and 4 pts (8.7%) had 3 organ involvement. 11 pts (23.9%) had heart and 35 pts (76.1%) had kidney involvement. The median follow up from the time of diagnosis was 22.4 months and from time of auto HCT was 16.7 months. High dose Melphalan dose was 200mg/m2 in 24 pts (52%) and 140mg/m2 in 22 (47.8%). There were 4 early deaths and 4 pts whose follow up was less than 3 months and their response was not assessed. Out of the 38 evaluable patients, the post-transplant organ responses were as follows ≥PR 25(66%), ≥stable disease 35(92%) (Table2). The hematologic responses were: CR=5 (13%), ≥VGPR=10(26%), ≥PR=26 (68%), ≥SD=37(97%). One patient had progressive disease. There was a correlation between organ response and hematologic response (chi square;p<10-3). The day-100 treatment related mortality (TRM) was 8.7% and 1-yr TRM was 13%. The median progression-free (PFS) and overall survival (OS) from auto HCT was 73.8 months and not reached (from transplant). The median PFS and OS from diagnosis were 93 months and 59.8 months respectively. In multivariate analysis, heart involvement (p=0.01), female sex (p=0.011), age ≥60 years (p=0.002), bone marrow plasma cells≥10% (p=0.043) and Beta-2 microglobulin>3.5mg/l (p=0.02) were associated with poor OS. Improved OS correlated with organ response (52.6 vs 11.4 months; p=0.01) and hematologic response (52.6 vs.6.1months; p=0.002). Hemoglobin <10 g/dl (p=0.047), bone marrow plasma cells≥10% (p=0.043) and age≥60 years (p=0.075) were associated with shorter PFS. Hematologc response (p=0.48) and organ response (p=0.12) were not associated with improved PFS. Conclusion: In this analysis the outcome of patients with primary systemic AL amyloidosis was durable with auto HCT with acceptable mortality risk and improved survival. Disclosures: No relevant conflicts of interest to declare.

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