Outcomes of autologous stem cell transplant for cardiac AL-amyloidosis and cardiac light chain deposition disease

2019 ◽  
Vol 26 (5) ◽  
pp. 1128-1133
Author(s):  
Al-Ola A Abdallah ◽  
Daisy Alapat ◽  
Varinder Kaur ◽  
Shebli Atrash
Keyword(s):  
Stem Cell ◽  
Light Chain ◽  
Cardiac Amyloidosis ◽  
Stem Cell Transplant ◽  
Al Amyloidosis ◽  
Cell Transplant ◽  
Hematopoietic Stem ◽  
Light Chain Deposition Disease ◽  
Deposition Disease ◽  
Light Chain Deposition

Introduction Cardiac amyloidosis and light chain deposition disease (LCDD) are the most common cause of death in AL amyloidosis or LCDD. Methods Our multiple myeloma database identified 50 patients with cardiac amyloidosis or LCDD between January 2004 and January 2013. Descriptive analyses were performed on available data for patient characteristics, disease course, and outcomes. Results The median age at diagnosis was 61 years for those who received autologous hematopoietic stem cell transplant (ASCT) and 71 years for those who received only bortezomib-based chemotherapy; 62.5% (n = 30) of patients had elevated levels of NT-proBNP ≥323 ng/L, and 29.2% (n = 14) of patients had an elevated cTnT ≥0.1 µg/L. Echocardiogram findings showed a speckled appearance in 18% (n = 9) of patients, and 60% (n = 30) of patients had an increased diastolic intra-ventricular septum (IVSD) thickness measuring ≥1.3 cm; 64.3% (n = 18) of patients who underwent cardiac MRI showed subendocardial enhancement. Out of 48 patients who received treatment, 37 patients were diagnosed with cardiac amyloidosis and 11 patients were diagnosed with cardiac LCDD. Twenty-eight patients (75.7%) with cardiac amyloidosis received ASCT, compared to 34.3% (n = 9) patients who were ineligible for ASCT and received chemotherapy only. Patients who underwent ASCT had a median OS of 4.48 years compared to 1.82 years (p = 0.69) for those receiving chemotherapy alone. Conclusion Our single institution experience shows that ASCT is feasible for cardiac amyloidosis and/or cardiac LCDD. However, careful selection of proper patients and diligent supportive care are vital to decreasing transplant-related mortality.

Autologous stem cell transplant for light chain deposition disease: Incorporating bortezomib to the induction therapy

2012 ◽  
Vol 87 (8) ◽  
pp. 822-823 ◽  
Author(s):  
Victor H. Jimenez-Zepeda ◽  
Suzanne Trudel ◽  
Andrew Winter ◽  
Donna E. Reece ◽  
Christine Chen ◽  
...  
Keyword(s):  
Stem Cell ◽  
Induction Therapy ◽  
Light Chain ◽  
Stem Cell Transplant ◽  
Autologous Stem Cell Transplant ◽  
Cell Transplant ◽  
Light Chain Deposition Disease ◽  
Deposition Disease ◽  
Light Chain Deposition

Outcome of High Dose Melphalan with Autologous Hematopoietic Stem Cell Transplant In Myeloma Associated with AL Amyloidosis

Blood ◽  
2010 ◽  
Vol 116 (21) ◽  
pp. 2400-2400
Author(s):  
Simrit Parmar ◽  
Mubeen Khan ◽  
Gabriela Rondon ◽  
Nina Shah ◽  
Qaiser Bashir ◽  
...  
Keyword(s):  
Stem Cell ◽  
Hematopoietic Stem Cell ◽  
Research Funding ◽  
Hematopoietic Stem Cell Transplant ◽  
Stem Cell Transplant ◽  
High Dose ◽  
Al Amyloidosis ◽  
Cell Transplant ◽  
Hematopoietic Stem ◽  
High Dose Melphalan

Abstract Abstract 2400 Background: Approximately 10% of patients with multiple myeloma (MM) have clinically overt primary systemic light-chain (AL) amyloidosis, and about 30% have concurrent occult AL amyloidosis. The impact of concurrent AL amyloidosis on the prognosis of myeloma is not well known. High-dose melphalan followed by autologous hematopoietic stem cell transplant (auto HCT) has shown significant activity in both MM and AL amyloidosis. Methods: We performed a retrospective analysis of patients who had concurrent MM and AL amyloidosis and underwent auto HSCT with high dose Melphalan at MDACC between 01/1998 to 05/2010. We identified 41 patients with concurrent MM and AL amyloidosis. Patient characteristics are summarized in Table 1. Twenty -six patients had occult AL amyloid, while 15 had clinically overt disease. Results: Median age at auto HSCT was 56 years (39-77), 58.5% being male with median follow up of 58.7 months from the time of diagnosis and 42.5 months from auto HCT. The median time from diagnosis to auto HCT was 8.9 mos (2.7-102.4 mos). 39% had Salmon Durie Stage III disease and 36.6% had more than one involved site at the time of transplant.Cytogenetic abnormalities were detected in 24.4% of patients. Post transplant hematologic responses were as follows: ≥CR=10 (24%), ≥VGPR=16 (39%), >PR=33 (80.5%), ≥stable disease= 40 (97.6%). Among the patients with overt organ involvement, one had early death. Of the 15 evaluable patients, organ responses were scored using the published consensus guidelines for amyloidosis and were as follows: PR=5 (33.3%), ≥SD=7 (46.7%). No correlation was seen between organ response and hematologic response. The 100-day treatment related mortality (TRM) was 0 and 1-year TRM of 2.4% which is comparable to patients transplanted for MM alone at our center. The median progression-free (PFS) and overall survival (OS) from auto HCT were 33.8 and 58.3 months, respectively.The median PFS and OS from diagnosis were 49.8 and 96 mos, respectively. In multivariate analysis, creatinine ≥ 2mg/dl was associated with a shorter PFS (p=0.043) and hemoglobin <10g/dl showed a trend towards a shorter PFS (p=0.093). None of these variables (Hb <10g/dl, Age>60yrs, Creatinine≥2mg/dl, B2M >3.5mg/l, BM plasma cells>30%) emerged as significant predictors of OS. There was no significant difference in outcome between patients with occult or symptomatic AL amyloidosis for OS (p=0.24) or PFS (P=0.9) Conclusion: In this analysis the outcome of patients with concurrent MM and AL amyloidosis was comparable to patients with MM alone. We believe these patients are acceptable candidates for auto HCT. Disclosures: Shah: Celgene: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; Millenium: Research Funding; Novartis: Research Funding. Weber: novartis-unpaid consultant: Consultancy; Merck- unpaid consultant: Consultancy; celgene- none for at least 2 years: Honoraria; millenium-none for 2 years: Honoraria; celgene, Millenium, Merck: Research Funding. Orlowski: Celgene: Consultancy, Research Funding; Millennium Pharmaceuticals, Inc.: Consultancy, Research Funding.

Outcomes of ASCT for cardiac AL-amyloidosis and cardiac light chain deposition disease.

2015 ◽  
Vol 33 (15_suppl) ◽  
pp. 7035-7035
Author(s):  
Al-Ola A. Abdallah ◽  
Shebli Atrash ◽  
Aziz Bakhous ◽  
Daisy Alapat ◽  
Maurizio Zangari
Keyword(s):  
Light Chain ◽  
Al Amyloidosis ◽  
Light Chain Deposition Disease ◽  
Deposition Disease ◽  
Light Chain Deposition

scholarly journals Hematologic Responses in Patients with Heavily Pretreated Light Chain Deposition Disease (LCDD) Receiving Daratumumab

Blood ◽  
2018 ◽  
Vol 132 (Supplement 1) ◽  
pp. 1985-1985
Author(s):  
Paolo Milani ◽  
Marco Basset ◽  
Andrea Foli ◽  
Giampaolo Merlini ◽  
Giovanni Palladini
Keyword(s):  
Partial Response ◽  
Light Chain ◽  
Cell Transplant ◽  
Light Chain Deposition Disease ◽  
Hematologic Response ◽  
Deposition Disease ◽  
Heavily Pretreated ◽  
Renal Progression ◽  
Line Of Therapy ◽  
Light Chain Deposition

Abstract Introduction: The monoclonal antibody daratumumab showed high response rates and a good safety profile in multiple myeloma and is being evaluated in clinical trials in AL amyloidosis. Light chain deposition disease (LCDD) is a rare monoclonal gammopathy of renal significance. Treatment directed against the underlying plasma cell clone can prevent renal progression. Bortezomib is commonly used upfront in these patients and daratumumab may represent a powerful novel option. Methods: We report the outcome of six patients with refractory light chain deposition disease (LCDD) treated with daratumumab at the Amyloidosis Research and Treatment Center of Pavia. All patients gave written informed consent. Hematologic response was assessed according to the International Society of Amyloidosis criteria. Results: Six patients (5 males and 1 female) received daratumumab intravenously at 16 mg/kg weekly for 8 weeks, followed by every other week infusions for 8 doses and then monthly infusions. Patients' clinical characteristics are reported in Table 1. All patients received daratumumab single agent except one who was treated with daratumumb and bortezomib combination (this patient received only 1 prior line of therapy). All patients were refractory to the last line of therapy. All patients received at least two months of therapy. All patients were previously treated with bortezomib, pomalidomide was used in 4 cases, lenalidomide, thalidomide and bendamustine in 2 cases each, and autologous stem cell transplant was performed in 4 subjects. The median time from LCDD diagnosis to daratumumab initiation was 8.3 years (range 8 - 147 months). Five of the 6 patients obtained hematologic response with at least a reduction of 50% of the dFLC value (partial response). Three patients obtained a very good partial response (dFLC <40 mg/L). The estimated glomerular filtration rate improved in one subject (from 30 to 45 mL/min per 1.73 m2) and in all the others remained stable. In 2 subjects treatment was temporarily discontinued due to pneumonia. Conclusions: This is the first report of the use of daratumumab in LCDD. This antibody yielded rapid and significant hematologic responses in five of six heavily pretreated patients with this disease, preventing renal progression. Daratumumab represents a promising option for these patients and larger, international studies are warranted. Disclosures Merlini: Akcea: Consultancy; Ionis: Consultancy; Prothena: Consultancy; Millenium: Consultancy; Janssen: Consultancy; Pfizer: Consultancy. Palladini:Celgene: Other: Travel support; Janssen: Membership on an entity's Board of Directors or advisory committees; Prothena: Honoraria.

Coincident remission of ankylosing spondylitis after autologous stem cell transplantation for multiple myeloma

2020 ◽  
pp. 107815522092775
Author(s):  
Hira Shaikh ◽  
Veli Bakalov ◽  
Soorih Shaikh ◽  
Ahmed Khattab ◽  
Santhosh Sadashiv
Keyword(s):  
Multiple Myeloma ◽  
Stem Cell ◽  
Ankylosing Spondylitis ◽  
Hematopoietic Stem Cell ◽  
Light Chain ◽  
Hematopoietic Stem Cell Transplant ◽  
Stem Cell Transplant ◽  
Cell Transplant ◽  
Hematopoietic Stem ◽  
Post Transplant

Introduction Ankylosing spondylitis is an autoimmune disease with chronic inflammation of the spine and sacroiliac joints that is commonly treated with immunosuppressants including disease-modifying antirheumatic drugs and anti-tumor necrosis factor alpha therapy. Case report A 75-year-old female with active ankylosing spondylitis on treatment with etanercept was referred to us for newly diagnosed IgG kappa free light chain multiple myeloma. After failing induction with revlimid, bortezomib, and dexamethasone, she was initiated on carfilzomib. Following the achievement of adequate response to induction, she underwent an autologous hematopoietic stem cell transplant selected for CD34+ cells with melphalan 200mg/m2 conditioning regimen. Given high-risk cytogenetics, i.e. monosomy 17 (17p) and hypodiploidy, she received two cycles of carfilzomib consolidation post-transplant. The patient tolerated the transplant well with successful engraftment and achieved complete remission of multiple myeloma with no detectable M spike, negative immunofixation study, and normalization of light chain ratio. While being off etanercept since the transplant, she noticed complete relief from joint pains related to her ankylosing spondylitis without a need to use the pain-relieving medications. Management and outcome: The patient has sustained remission of ankylosing spondylitis for two years post-transplant without flares or symptoms. She continues to remain off immunosuppressants. Discussion Although our patient had a coincident and unprecedented resolution of ankylosing spondylitis after receiving the hematopoietic stem cell transplant, this case consolidates the idea of transplant as a potential treatment option for ankylosing spondylitis and other rheumatological conditions.

Bortezomib-Dexamethasone As Induction Therapy for Light Chain Deposition Disease (LCDD): A Single Center Experience

Blood ◽  
2012 ◽  
Vol 120 (21) ◽  
pp. 5027-5027
Author(s):  
Federica Lessi ◽  
Monica Castelli ◽  
Livio Trentin ◽  
Sara Altinier ◽  
Francesco Piazza ◽  
...  
Keyword(s):  
Renal Function ◽  
Stem Cell ◽  
Plasma Cell ◽  
Induction Therapy ◽  
Light Chain ◽  
High Dose ◽  
Light Chain Deposition Disease ◽  
Deposition Disease ◽  
Osteolytic Bone Disease ◽  
Light Chain Deposition

Abstract Abstract 5027 Background: LCDD is a rare plasma cell dyscrasia characterized by deposition of immunoglobulin light chain in kidneys and, occasionally, in other organs such as liver and heart. Most patients present with rapidly deteriorating renal function and nephrotic proteinuria. There is no standard treatment for LCDD. High dose dexametasone (HDD) with or without alkylating agents and high dose melphalan (HDM) followed by autologous stem cell transplantation (ASCT) have been used, the latter with better results. Recently the combination therapy with Bortezomib-Dexametasone (BD) has been used in small series of patients and has shown promising results. Here we report on four patients with LCDD treated in our center from September 2010 to September 2011 with BD as induction therapy. Patients and Methods: The characteristics of the patients are shown in Table 1. Three patients were male; the median age was 44. 5 years (range 37–64 years). Two patients had more than 20% bone marrow plasma cell count with no evidence of active multiple myeloma (MM) defined by osteolytic bone disease, hypercalcemia or myeloma cast nephropaty. All patients had renal biopsy with histologic and immunofluorescence studies. In all patients except one, the diagnosis was confirmed by electron microscopy examination. One patient was therapy naive and three patients were refractory to HDD. All patients but one presented with impaired renal function and all of them showed nephrotic albuminuria. Serum free light chains values (sFLC) were high in all patients, with abnormal kappa to lambda ratio (R k/λ). Noteworthy, in three patients serum immunofixation electrophoresis did not succeed in detecting the circulating monoclonal light chain. Patients were given Bortezomib (1. 3 mg/m2days 1, 4, 8 and 11) and Dexamethasone (40 mg days 1–4) every 21 days, for three to six cycles. Results: Two patients achieved normalization of R k/λ. One patient achieved reduction of more than 50% of involved sFLC and reduction of more than 50% of the M protein after three cycles. One patient had progressive disease. None of the responding patients with renal impairment achieved improvement of the renal function, but all responding patients showed reduction of more than 50% of initial albuminuria. After BD one patient achieved hematological CR, one VGPR and one PR (Gertz MA et al., Amyloid 2010). All responding patients were eligible for ASCT. Two patients underwent stem cell mobilization with cyclophosphamide 4 g/m2; one patient was mobilized with G-CSF alone. Melphalan dose was reduced to 140 mg/m2in the only patient undergoing hemodyalisis. There were no complications related to stem cell harvest and engraftment (only one patient showed a late platelet engraftment). After ASCT two patients achieved at least VGPR; one patient achieved a PR and he underwent second ASCT achieving again a PR. Dose reduction of Bortezomib was required in two patients because of grade 2 neuropathy. Conclusions: BD is feasible and effective in LCDD patients, and it can be used as an induction regimen before ASCT. Disclosures: Off Label Use: Bortezomib for light chain deposition disease.

scholarly journals Treatment of Light Chain Deposition Disease Using Bortezomib-Based Regimen Followed by Thalidomide-Based Regimen in a Saudi Male

2016 ◽  
Vol 2016 ◽  
pp. 1-4 ◽  
Author(s):  
Bappa Adamu ◽  
Mushabab Al-Ghamdi ◽  
Mustafa Ahmad ◽  
Khaled O. Alsaad
Keyword(s):  
Light Chain ◽  
Light Chains ◽  
Cell Transplant ◽  
Free Light Chains ◽  
Light Chain Deposition Disease ◽  
Serum Free ◽  
Deposition Disease ◽  
Serum Free Light Chains ◽  
Light Chain Deposition ◽  
Saudi Male

Light chain deposition disease (LCDD) is a rare illness with, as yet, no clear evidence-based guidelines for its treatment. To the best of our knowledge, LCDD has not been previously reported from Saudi Arabia. We present in this report, a 38-year-old Saudi male who presented with clinical features suggestive of hypertensive nephropathy but kidney biopsy later revealed the diagnosis of LCDD. His serum creatinine at presentation was 297 μmol/L which came down to 194 μmol/L on treatment with Bortezomib, Cyclophosphamide and Dexamethasone. His 24-hour protein excretion at presentation was 6 g/L which also came down to less than 1 g/day. He was later placed on Cyclophosphamide, Thalidomide, and Dexamethasone regimen because of persistent high titres of serum free light chains. He went into remission with undetectable serum free light chains and remained so for three years at the time of writing this report. We conclude that LCDD, though rare, does occur in Saudi population. The treatment of LCDD is challenging but the use of Bortezomib, a proteosome inhibitor, is promising. However, suboptimal response may require further treatment with other therapeutic options such as chemotherapy with alkylating agents or high-dose Melphalan with autologous stem cell transplant.

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