scholarly journals Effect of Severe Hypoalbuminemia on Myelosuppression and Other Toxicities of High Dose Melphalan and Autologous Stem Cell Transplantation in AL Amyloidosis Patients

Blood ◽  
2014 ◽  
Vol 124 (21) ◽  
pp. 5906-5906
Author(s):  
Robert Meehan ◽  
David Seldin ◽  
John Mark Sloan ◽  
Karen Quillen ◽  
Dina Brauneis ◽  
...  
Keyword(s):  
Stem Cell ◽  
Median Time ◽  
Stem Cell Transplant ◽  
Conflicts Of Interest ◽  
Autologous Stem Cell Transplant ◽  
Albumin Level ◽  
High Dose ◽  
Al Amyloidosis ◽  
Cell Transplant ◽  
Peripheral Blood Stem Cells

Abstract Background: Treatment of AL amyloidosis with high dose intravenous melphalan followed by autologous stem cell transplant (HDM/SCT) is effective in inducing hematologic and clinical remissions associated with prolonged survival. The major toxicities are myelosuppression and GI side effects. Studies have shown that ~75% of melphalan in the blood is bound to plasma proteins, with ~25% free. We hypothesized that AL patients with severe nephrotic syndrome and profound hypoalbuminemia might have a higher fraction of free melphalan, a higher effective dose, and greater toxicity of treatment. Methods: Patients with AL amyloidosis and severe hypoalbuminemia, defined as serum albumin level of < 2 g/dL, treated from 2011 to 2013, were studied retrospectively. The stem cell transplant database was queried for dose of HDM, treatment-related complications, and days of neutrophil and platelet engraftment after SCT. Results: Of 71 patients with AL amyloidosis who underwent HDM/SCT between Jan 2011 and Dec 2013, 12 patients had severe hypoalbuminemia. Of these, 5 received full HDM at 200 mg/m2 and 7 received modified HDM at 140 mg/m2. All patients received GCSF mobilized peripheral blood stem cells following HDM, with a median stem cell dose of CD34+ cells 8.1 x 106/kg (range, 4.0 to 12.2). The median time to engraftment of neutrophils was 11 days, and not statistically different based upon melphalan dose. The median time to platelet engraftment was 13 days, and also did not differ significantly by dose. These times were similar to controls without severe hypoalbuminemia. Grade 4 toxicities were observed in 2 of 7 patients with modified HDM/SCT and 1 of 5 patients with full HDM/SCT. Conclusions: These data suggest that patients with severe hypoalbuminemia do not have more prolonged myelosuppression or increased non-hematologic toxicities compared to other patients. In this retrospective study, we did not measure free melphalan concentrations in the blood. However, these data suggest that patients with severe hypoalbuminemia do not require adjustment of melphalan dosing. Disclosures No relevant conflicts of interest to declare.

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.

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.

scholarly journals Long-Term Results of Cytarabine-Containing Induction Followed By Consolidation with Autologous Stem Cell Transplant and Rituximab Maintenance As Primary Treatment for Mantle Cell Lymphoma

Blood ◽  
2015 ◽  
Vol 126 (23) ◽  
pp. 1995-1995
Author(s):  
Umberto Falcone ◽  
Shaheena Bashir ◽  
Khalil Al-Farsi ◽  
Laurie Watkins ◽  
C. Denise Turvey ◽  
...  
Keyword(s):  
Stem Cell ◽  
Median Time ◽  
Stem Cell Transplant ◽  
Autologous Stem Cell Transplant ◽  
High Dose ◽  
Cell Transplant ◽  
First Line ◽  
Rituximab Maintenance ◽  
Cd34 Cells ◽  
Mantle Cell

Abstract Introduction: Mantle cell lymphoma (MCL) often follows an aggressive course and remains incurable with standard therapies. First-line chemotherapy followed by consolidation with high-dose chemotherapy (HDT) and autologous stem cell transplant (ASCT) has become a standard of care in eligible patients (pts). As relapse remains the main cause of treatment failure, strategies such as intensifying induction therapy with high-dose cytarabine or adding rituximab maintenance (RM) have been tested to reduce the relapse rate (RR) post-ASCT. We evaluated the effect of the addition of cytarabine and RM on the outcome of pts undergoing ASCT. Methods: We conducted a retrospective analysis of consecutive MCL pts who underwent ASCT after first-line chemotherapy at the Princess Margaret Cancer Centre between 2000-2013. Pts received induction with CHOP, RCHOP, or RCHOP alternating with RDHAP (RCHOP/RDHAP), followed by HDT with or without total body irradiation (TBI). All pts had a documented response to induction using Cheson 1999 criteria. After ASCT, pts received maintenance with single-agent rituximab 375 mg/m2 or were simply observed. Results: 98 MCL pts were treated: median age was 56 years (36-66), 15 pts (15%) had blastoid or pleomorphic subtype, 85 pts (87%) had stage IV disease. MIPI was high risk in 18 pts (19%). Induction therapy: CHOP 14 pts (14%), RCHOP 57 (58%), and RCHOP/RDHAP 27 (28%). After induction CR was obtained in 44%, PR in 56% pts. CR rates were: CHOP 7 (50%), RCHOP 25 (44%), RCHOP/RDHAP 12 (44%) (P=ns). 89% pts had collected > 5*106 CD34/kg after RCHOP, and 78% after RCHOP/RDHAP (P=ns). Overall 66/98 pts (67%) had > 5*106 CD34/kg collected with 1 apheresis (Table 1). HDT was melphalan+etoposide for 63% pts, cytarabine+melphalan for 31% pts; 77 (79%) also received TBI. Median time from diagnosis to ASCT was 7.5 months (2.5, 33.4). Post-ASCT responses: CR 92 pts (94%), PR 4 (4%), 2 (2%) PD. Median time to ANC ≥0.5 were 10 days (CHOP), 11 days (RCHOP), and 11 days (RCHOP/RDHAP), while median days to PLT≥20 were 9 (CHOP), 11.5 (RCHOP), and 13 (RCHOP/RDHAP). Post-ASCT, 31% of pts had normal blood counts at 3 months which improved to 52% at 1 year post-ASCT. Maintenance data were available for 95/98 pts. RM was given to 72 pts (74%). Median follow-up from date of transplant for the entire cohort was 3.22 years (range 0.7 - 14.1). The 2-year and 5-year PFS were 85.8% (76.7-91.5) and 52.2% (37.7-64.7), respectively. 32 pts relapsed after ASCT (32.65%). Relapse occurred in 3 (11%) pts after RCHOP/RDHAP, 19 (33%) after RCHOP, and 10 (71%) after CHOP. Median time to relapse was 9 years (95%CI: 4.7-NR). 2-year and 5-year RR were 14.54% and 41.65%, respectively. Median OS was 9.15 years (95%CI: 7.3-NR), 2-year OS was 88.8% (80.2-93.8), and 5-year OS was 74.9% (61.7-84.2%). For patients observed without treatment post-ASCT, median PFS was 2.87 years (1.22-4.63) and median OS 5.19 years (1.66-NR), while for those receiving RM, PFS was 9.06 years (4.97-NR, p<0.001) and median OS has not yet been reached (7.30- NR, p=0.009). Conclusions: Response rate and PFS were similar between different induction regimens. The outcomes of responding pts following ASCT appear superior to previous strategies. Our patients enjoyed a very long PFS and median OS is surprisingly long as well. Within the limits of a retrospective study, our data support the use of rituximab maintenance, showing a significant benefit in both PFS and OS. Table 1. ASCT data Stem cell collection CHOP RCHOP RCHOP/RDHAP P value Pts collecting > 2x106 /Kg CD34+ cells in 1 day 4/14 (29%) 44/57 (77%) 17/27 (67%) 0.002 Pts collecting 2-5 x106 /Kg CD34+ cells N/A 6/57 (11%) 6/27 (22%) Pts collecting >5 x106 /Kg CD34+ cells N/A 51/57 (89%) 21/27 (78%) 0.153 Engraftment median (range) Days to ANC ≥ 0.5 10 (9,11) 11 (9, 12) 11 (9, 12) Pts with ANC ≥ 0.5 ≤ 11 days 13/13 (100%) 45/52 (87%) 21/25 (84%) 0.33 Days to PLT ≥ 20 9 (7, 15) 11.5 (9, 17) 13 (9, 26) Pts with PLT ≥ 20 ≤ 12 days 12/13 (92%) 37/52 (71%) 8/25 (32%) 0.0001* Days from ASCT to discharge 13 (11,26) 14 (11,30) 13 (11,23) PTs requiring RBC Transfusions 11 (79%) 43 (75%) 22 (81%) 0.821 Number of RBC Transfusions 2 (0, 4) 2 (0, 7) 3(0, 6) Pts requiring PLT Transfusions 12 (86%) 52 (93%) 25 (93%) 0.759 Number of PLT Transfusions 1 (0, 4) 2 (1, 9) 3 (1, 5) * comparison CHOP Vs R-CHOP: not significant, p=0.113 Legend. ASCT: autologous stem cell transplant; Pts: patients; ANC: absolute neutrophils count; PLTs: platelets; RBC: red blood cells. Disclosures Kuruvilla: Hoffmann LaRoche: Consultancy, Honoraria, Research Funding; Seattle Genetics: Consultancy, Honoraria; Gilead: Consultancy; Janssen: Consultancy, Honoraria; Merck: Honoraria; Bristol-Myers Squibb: Honoraria; Lundbeck: Honoraria; Karyopharm: Honoraria.

131I-Metaiodobenzylguanidine (131I-MIBG) double infusion with autologous stem cell transplant for neuroblastoma: A New Approaches to Neuroblastoma Therapy (NANT) study

2006 ◽  
Vol 24 (18_suppl) ◽  
pp. 9011-9011
Author(s):  
K. K. Matthay ◽  
A. Quach ◽  
J. Huberty ◽  
B. Franc ◽  
S. Groshen ◽  
...  
Keyword(s):  
Stem Cell ◽  
Median Time ◽  
Stem Cell Transplant ◽  
Maximum Tolerated Dose ◽  
Autologous Stem Cell Transplant ◽  
High Dose ◽  
Hematologic Toxicity ◽  
Cell Transplant ◽  
Red Marrow ◽  
Heavily Pretreated

9011 Background: 131I-MIBG provides targeted radiotherapy with >30% response in refractory neuroblastoma, but the activity infused is limited by radiation safety and hematologic toxicity. The goal was to determine the maximum tolerated dose of 131I-MIBG in two consecutive infusions at a 2-week interval, supported by autologous stem cell transplant (ASCT) 2 weeks after the second dose. Methods: The 131I-MIBG was escalated in a 3+3 Phase I trial design, with levels calculated by total red marrow radiation index (RMI) from the double infusion. The first infusion of 131I-MIBG was 12, 15, 18 and 21 mCi/kg for levels 1, 2, 3 and 4 respectively. Using detailed dosimetry, the second infusion was adjusted to achieve the target RMI, except at Level 4, where the second infusion was capped at 21 mCi/kg. Results: Twenty-one patients were enrolled at Level 1–4, with 18 evaluable for toxicity. Median age at enrollment was 7 years, all were heavily pretreated, including 12 with prior high dose therapy and ASCT, and 12 patients had bone marrow tumor. Cumulative 131I-MIBG given to achieve the target RMI ranged from 18 mci/kg to 49 mCi/kg. RMI delivered per mCi of MIBG decreased in 15/19 patients by mean of 0.21 cGy/mCi with the second infusion. Hematologic toxicity was acceptable, with median time to ANC>500 after ASCT of 13 (4–27) days. Platelet transfusion was required in 15/18 patients, with median time to platelet independence of 18 (6–47) days after ASCT. There were no non-hematologic toxicities above grade 2 attributed to therapy, though 9 patients had grade 1–2 elevations of transaminase, and 1 had grade 2 hypothyroidism. Responses in 17 evaluable patients included 1 PR, 4 MR, 6 SD, and 6 PD. Eleven patients are alive at median of 361 days (46–483); 5 died of PD and 1 of unrelated toxicity. Conclusion: The lack of toxicity with this approach allowed dramatic dose intensification of 131I-MIBG, with minimal toxicity and the possibility of improved response. [Table: see text] No significant financial relationships to disclose.

scholarly journals Sequential response-driven bortezomib-based therapy followed by autologous stem cell transplant in AL amyloidosis

2020 ◽  
Vol 4 (17) ◽  
pp. 4175-4179
Author(s):  
Marco Basset ◽  
Paolo Milani ◽  
Mario Nuvolone ◽  
Francesca Benigna ◽  
Lara Rodigari ◽  
...  
Keyword(s):  
Stem Cell ◽  
Partial Response ◽  
Stem Cell Transplant ◽  
Complete Response ◽  
Autologous Stem Cell Transplant ◽  
Survival Duration ◽  
Al Amyloidosis ◽  
Cell Transplant ◽  
Duration Of Response ◽  
Landmark Analyses

Abstract Autologous stem cell transplant (ASCT) is highly effective in selected patients with light chain (AL) amyloidosis. Bortezomib, preceding or following ASCT, improves responses. Satisfactory responses, including at least a partial response, very good partial response (VGPR) with organ response, or complete response, can be observed after induction therapy alone. We report 139 patients treated upfront with cyclophosphamide/bortezomib/dexamethasone (CyBorD), followed by ASCT only if response was unsatisfactory. Only 1 treatment-related death was observed. After CyBorD, hematologic response (HR) rate was 68% (VGPR or better, 51%), with 45% satisfactory responses. Transplant was performed in 55 (40%) subjects and resulted in an 80% HR rate (65% ≥ VGPR). Five-year survival was 86% and 84% in patients treated with ASCT or CyBorD alone, respectively (P = .438). Also, 6- and 12- month landmark analyses did not show differences in survival. Duration of response was not different in the 2 groups (60 vs 49 months; P = .670). Twenty-one (15%) patients with an unsatisfactory response to CyBorD could not undergo ASCT because of ineligibility or refusal; instead, they received rescue chemotherapy, with HR in 38% of cases and 51% 5-year survival. This sequential response-driven approach, offering ASCT to patients who do not attain satisfactory response to upfront CyBorD, is very safe and effective in AL amyloidosis.

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