scholarly journals High Dose Melphalan Followed By Autologous Stem Cell Transplant in AL Amyloidosis: a Single-Center Experience

Blood ◽  
2014 ◽  
Vol 124 (21) ◽  
pp. 5909-5909
Author(s):  
Mariella D'Adda ◽  
Francesca Schieppati ◽  
Samantha Ferrari ◽  
Claudia Crippa ◽  
Annalisa Peli ◽  
...  
Keyword(s):  
Cardiac Troponin ◽  
Stem Cell Transplant ◽  
Troponin T ◽  
Autologous Stem Cell Transplant ◽  
High Dose ◽  
Al Amyloidosis ◽  
Cell Transplant ◽  
Single Center Experience ◽  
High Dose Melphalan

Abstract INTRODUCTION: high-dose melphalan (HDM) followed by autologous stem cell transplant (ASCT) has been routinely used as a treatment option for systemic light chain AL amyloisosis since the first report in mid-1990s. The high treatment-related mortality (death before post-transplant day 100) reported in literature (11-40% in different papers) has decreased over the last years with the improvement in patient selection. Particularly, in the largest Mayo Clinic series of 422 subjects, patients with cardiac troponin-T < 0.06 ng/L and NT-proBNP < 5000 ng/L had TRM < 1%; besides, patients achieving hematologic complete response/very good partial remission (CR/VGPR) had superior overall survival than those achieving hematologic partial response (PR) and no response. Here we report our single-center experience of 14 ASCT performed in 10 patients between 2007 and 2014. PATIENTS AND METHODS: the median age at the time of ASCT was 58 years (range 44-68). Five patients had 2 or more involved organs. All 10 patients had: normal troponin-I value, NT-proBNP < 5000 ng/L, PS 0-1, cardiac ejection fraction over 50%, CO diffusion capacity over 50%; only one had creatinine clearance < 50 ml/min. Three patients collected stem cells after cyclophosphamide (1,5 g/m^2), the others after G-CSF alone. Four patients proceeded directly to ASCT after diagnosis, 3 received CyBorD and 3 other induction regimen (5 patients were non responders and 1 was in hematologic PR after “induction therapy” before HDM). Patients received melphalan 200 mg/m^2 (9 ASCT) or dose adjusted HDM (100-140 mg/m^2, 5 ASCT), depending on clinical decision. Four patients received double ASCT. RESULTS: median follow up is 48 months (range 0,5-80); all patients were alive at the last visit. Of nine evaluable patients (1 patient too early), overall hematologic and organ response rate after ASCT were 78% and 45%. Only 1 of 4 patients with double ASCT improved response after the second course (this patient maintains a hematologic CR without organ involvement after 80 months of follow up). Median hospitalization for ASCT was 24 days (range 17-45), without any threatening-life side effect. Six of 9 evaluable patients needed a 2ndline therapy for progressive disease after a median follow up of 24 months (range 13-52): 4 of them had achieved hematologic PR after ASCT, 1 patient achieved hematologic VGPR and 1 had no hematologic response. Three patients are in follow up without other therapy after ASCT (2 hematologic CR and 1 non response). CONCLUSION: HDM followed by ASCT is a very effective treatment option in AL-amyloidosis, which may be effective even in patients non responding to first-line treatment with non myeloablative drugs. According to the data of the literature, our experience suggests that a careful selection of patients is critical for good outcomes and that particular cardiac biomarkers (cardiac troponin-T < 0.06 ng/L and NT-proBNP < 5000 ng/L) are useful to guide the choice of therapy. Furthermore, consolidation therapy (IMiDs and proteasome inhibitors) should be considered for patients who do not obtain at least a VGPR/CR after HDM. 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.

Once Weekly Subcutaneous Bortezomib, Cyclophosphamide, and Dexamethasone As Induction Therapy for All AL Amyloidosis

Blood ◽  
2016 ◽  
Vol 128 (22) ◽  
pp. 5813-5813 ◽  
Author(s):  
Hashim Abbas ◽  
Lisa A. Rybicki ◽  
Frederic J. Reu ◽  
Christy Samaras ◽  
Mitchell R. Smith ◽  
...  
Keyword(s):  
Research Funding ◽  
Stem Cell Transplant ◽  
Cleveland Clinic ◽  
Autologous Stem Cell Transplant ◽  
High Dose ◽  
Al Amyloidosis ◽  
Cell Transplant ◽  
Probability Of Survival ◽  
Hematologic Response ◽  
High Dose Melphalan

Abstract High dose melphalan followed by autologous stem cell transplant is the standard of care for all transplant eligible AL amyloidosis patients. Due to medical insurance approvals and pre-transplant evaluation, treatment is delayed by months. Given that there are many patients who respond quickly to bortezomib based regimens, we have adopted a bortezomib based induction regimen in an attempt to prevent early progression or death due to amyloidosis. Materials and methods: All AL amyloidosis patients treated at the Cleveland Clinic who received bortezomib 1.3 mg/m2 subcutaneous, cyclophosphamide 300mg/m2 (dose cap at 500 mg) intravenous or oral, and dexamethasone 20 mg intravenous or oral (CyBorD) on day 1,8, and15, of a 28 day cycle were included in this analysis. Patient information was obtained from an institutional review board approved database and electronic medical record review. Hematologic response was assessed every 28 days. Transplant eligible patients who achieved early complete hematologic response (CR) completed up to 6 cycles of CyBorD followed by high dose melphalan and autologous stem cell transplant (ASCT). If there was no CR at the end of 2 cycles of therapy, patients underwent high dose melphalan and ASCT. Non- transplant eligible patients completed a planned 6 cycles of CyBorD. The primary outcome of the study was to assess overall survival (OS) of all AL amyloidosis patients by Kaplan-Meier estimate. The secondary outcomes were to assess the best hematologic response1, with CyBorD plus ASCT versus CyBorD alone and evaluate if any transplant eligible patients were unable to proceed to ASCT after receiving CyBorD. Results: With a median follow up of 30 months, patients who received CyBorD plus ASCT had a 92% probability of survival. Patients who received CyBorD alone had a 47 % probability of survival. All patients who were deemed transplant eligible at diagnosis underwent high dose melphalan and ASCT. The median NT-proBNP for patients who underwent ASCT was 305 pg/ml and for patients who were transplant ineligible was 6047 pg/ml. The best hematologic response in patients who received bortezomib based induction plus transplant was CR 71%, very good partial response (VGPR) 18%, stable disease (SD) 6%, and progressive disease (PD) 6%. Patients treated with CyBorD alone had a CR 56%, VGPR 6%, SD 19%, and PD 12%. Discussion: None of the transplant eligible patients were deemed transplant ineligible after the induction therapy. The OS was excellent for patients who underwent transplant. The percentage of CR in the transplant eligible patients compared favourably to historical reports of CR with ASCT alone. Only 12 % of patients undergoing ASCT failed to achieve a VGPR compared to 37% of patients with CyBorD alone. Certainly the transplant ineligible patients had severely compromised baseline cardiac function but despite that the probability of survival at 30 months was 47%. With this data, we plan to standardize bortezomib based induction AL amyloidosis treatment with a care path for the entire Cleveland Clinic health care system. Abbreviations: NT-proBNP (amino-terminal pro-B-type natriuretic peptide). References: 1. Palladini G, Dispenzieri A, Gertz MA, et al. New criteria for response to treatment in immunoglobulin light chain amyloidosis based on free light chain measurement and cardiac biomarkers: impact on survival outcomes. J Clin Oncol. 2012 Dec 20;30(36):4541-9 Figure 1 Probability of survival for all AL amyloidosis patients treated with CyBorD. Figure 1. Probability of survival for all AL amyloidosis patients treated with CyBorD. Disclosures Reu: Takeda: Research Funding; Novartis: Research Funding; Signal Genetics: Consultancy; Celgene: Research Funding. Smith:Genentech: Honoraria; Abbvie: Research Funding; Spectrum: Honoraria; Celgene: Honoraria. Valent:Takeda: Speakers Bureau; Celgene: Speakers Bureau.

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 and Treatments of Relapsed AL Amyloidosis Following Stem Cell Transplant

Blood ◽  
2012 ◽  
Vol 120 (21) ◽  
pp. 1858-1858 ◽  
Author(s):  
Rahma Warsame ◽  
Soo-Mee Bang ◽  
Shaji K. Kumar ◽  
Martha Q Lacy ◽  
Francis K Buadi ◽  
...  
Keyword(s):  
Stem Cell ◽  
Stem Cell Transplant ◽  
Plasma Cells ◽  
Conflicts Of Interest ◽  
Treatment Options ◽  
Autologous Stem Cell Transplant ◽  
Al Amyloidosis ◽  
Cell Transplant ◽  
Post Transplant

Abstract Abstract 1858 Systemic light chain amyloidosis (AL amyloidosis) is a condition where clonal plasma cells produce misfolded insoluble immunoglobulin light chains that deposit in various organs causing progressive organ dysfunction. Chemotherapy and autologous stem cell transplant (ASCT) when eligible is the standard treatment options for patients with AL amyloidosis. There are several studies who report long term outcomes of patient post ASCT. However, there is a paucity of literature describing the outcomes of patients who have received ASCT but have relapsed. We performed a retrospective study to assess the outcomes and treatment regimens employed following relapse after ASCT. Between 1996 and 2009, 410 patients received ASCT at the Mayo Clinic as first line therapy. Of those 410 patients 42 patients died within 3 months of transplant, 64 patients died without documented relapse, 158 patients were alive without documented progression, and 146 patients had documented progression. Those 146 patients are the subject of our study. The median time to hematologic relapse was 2 years (range: 0.2–15.5 years). At relapse, 59 patients were treated with IMiD based therapy, 36 with alkylator based therapy, 24 with bortezomib, 15 with steroids, and 5 with second ASCT. The respective hematologic response rates were 58%, 33%, 50%, 53%, and 60%. The remaining six patients were not evaluable for response for one other following reasons: organ transplants; no further therapy; inevaluable disease. With a median post relapse follow up of 3.6 years, the median overall survival (OS) from the first post ASCT relapse was 4.6 years. The median post transplant follow up was 6.1 years, the median OS for these patients was 7.3 years from the time of transplant. These data provide novel information about outcomes after SCT relapse, which should be useful not only for patients and doctors but also for investigators designing studies for salvage therapies post-transplant. Disclosures: No relevant conflicts of interest to declare.

scholarly journals Alternative Consolidation Strategy after High Dose Methotrexate, Rituximab and Temozolamide in Primary CNS Lymphoma - the Henry Ford Experience

Blood ◽  
2020 ◽  
Vol 136 (Supplement 1) ◽  
pp. 5-5
Author(s):  
Joyce Philip ◽  
Shivani Sharma ◽  
Vijayalakshmi Donthireddy
Keyword(s):  
Stem Cell ◽  
Stem Cell Transplant ◽  
Primary Cns Lymphoma ◽  
Autologous Stem Cell Transplant ◽  
Cns Lymphoma ◽  
High Dose ◽  
Cell Transplant ◽  
High Dose Methotrexate ◽  
Dose Methotrexate

Background: Treatment for primary CNS lymphoma involves a methotrexate-based induction therapy followed by consolidation. The optimal consolidation treatment after induction with a high dose Methotrexate (HD-MTX), Rituximab and Temozolomide regimen has not been fully established. The CALGB 50202 regimen using Etoposide and Cytarabine consolidation was associated with significant toxicity. We sought to review the results of alternative consolidation regimens and evaluate the progression free survival and overall survival. Methods: A retrospective cohort study was conducted to evaluate the efficacy of alternative consolidation regimens such as autologous stem cell transplant and HDMTx alone. Patients diagnosed with primary CNS lymphoma between November 2012 and March 2019 were identified. All patients received the same induction chemotherapy based on the CALGB 50202 protocol. Data was collected for baseline characteristics, progression free survival and overall survival. Results: 38 patients had a diagnosis of primary CNS lymphoma. 15 patients received treatment as per the CALBG 50202 induction protocol with high dose Methotrexate, Rituximab and Temozolomide. Of the 15 patients, 11 patients (69%) achieved a complete remission (CR) after induction therapy. 7 patients received an autologous stem cell transplant for consolidation, 5 patients received HD-MTX alone for consolidation and one patient was placed on Lenalidomide maintenance. 2 patients did not receive any consolidation therapy due to progressive disease and/or death. At a median follow up of 2.7 years for the entire cohort, median PFS was 31.7+ months and median OS was 32.5+ months. At a median follow up of 2.7 years for patients who were consolidated with an autologous stem cell transplant, median PFS and median OS was 27.2+ and 32.5+ months respectively. At a median follow up of 5.5 years for patients who were consolidated with treatments other than transplant, median PFS and OS was 65.6+ months. There were no deaths attributed to treatment related toxicity. To date, 4 patients of the entire cohort have died, with a median survival time among surviving patients of 3.6 years (range, 0.68-7.05 years). There were no deaths attributed to treatment related toxicity. Conclusion: Patients with primary CNS lymphoma who received induction therapy as per CALGB 50202 regimen and received alternative consolidation therapies with either autologous stem cell transplant or HD-MTX based consolidation achieved prolonged PFS and OS comparable if not superior to the Etoposide and Cytarabine consolidation. Results of the ongoing CALGB 51101 trial will determine the utility of EA consolidation. Disclosures No relevant conflicts of interest to declare.

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