scholarly journals Effect of Conditioning Regimen Dose Reduction in Obese Patients Undergoing Autologous Hematopoietic Cell Transplantation

2019 ◽  
Vol 25 (3) ◽  
pp. 480-487 ◽  
Author(s):  
Claudio G. Brunstein ◽  
Marcelo C. Pasquini ◽  
Soyoung Kim ◽  
Mingwei Fei ◽  
Kehinde Adekola ◽  
...  
Keyword(s):  
Dose Reduction ◽  
Cell Transplantation ◽  
Hematopoietic Cell Transplantation ◽  
Conditioning Regimen ◽  
Hematopoietic Cell ◽  
Obese Patients ◽  
Autologous Hematopoietic Cell Transplantation

Improved outcomes with maintenance therapy after salvage autologous hematopoietic cell transplantation (AHCT) in multiple myeloma: A CIBMTR study.

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. 8022-8022
Author(s):  
Oren Pasvolsky ◽  
Raphael Fraser ◽  
Noel Estrada-Merly ◽  
Moshe Yeshurun ◽  
Uri Rozovski ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Maintenance Therapy ◽  
Cell Transplantation ◽  
Hematopoietic Cell Transplantation ◽  
Univariate Analysis ◽  
Conditioning Regimen ◽  
Hematopoietic Cell ◽  
Improved Outcomes ◽  
Autologous Hematopoietic Cell Transplantation ◽  
Maintenance Group

8022 Background: Maintenance therapy in multiple myeloma (MM) after first autologous hematopoietic cell transplantation (AHCT1) is considered standard of care. Data regarding maintenance therapy after a salvage AHCT (AHCT2) in the setting of relapsed MM are scarce. Therefore, we used data from the Center for International Blood and Marrow Transplant Research (CIBMTR) registry to examine the use of maintenance therapy after AHCT2 in MM patients and its effect on post-transplant patient outcomes. Methods: We included US adult MM patients who underwent AHCT2 after melphalan conditioning regimen from 2010-2018, and excluded patients who underwent tandem transplants. Outcomes of interest included non-relapse mortality (NRM), relapse/progression (REL), progression-free and overall survival (PFS, OS). Cox proportional hazards models were developed to study the main effect (maintenance use) with other covariates of interest including age, sex, race, performance status, HCT-comorbidity index, MM subtype, stage, creatinine, cytogenetic, conditioning melphalan dose, disease status at transplant, and time from AHCT1 to AHCT2. Results: Of 522 patients, 342 received maintenance therapy and 180 did not after AHCT2. Baseline characteristics were similar between the two groups. Median follow up was 58 months in the maintenance group and 61.5 months in the no-maintenance group. Common maintenance regimens included immunomodulatory drugs (IMID)-lenalidomide (N = 145, 42%) or pomalidomide (N = 46, 13%) and proteasome inhibitor, bortezomib (N = 45, 13%). Univariate analysis showed superior outcomes at 5 years in maintenance compared to the no-maintenance group: NRM 2 (0.7-3.9)% vs 9.9 (5.9-14.9)%, p < 0.001, REL 70.2 (64.4-75.8)% vs 80.3 (73.6-86.3)%, p 0.003, PFS 27.8% (22.4-33.5) vs. 9.8% (5.5-15.2), p < 0.001, and OS 54% (47.5-60.5) vs 30.9% (23.2-39.2) p < 0.001, respectively. IMID-containing maintenance regimens were associated with an improved 5-year PFS and OS compared to other maintenance regimens. Use of maintenance therapy retained its association with improved outcomes in multivariate analysis, including NRM: hazard ratio (HR) 0.19 (0.08-0.44), p 0.0001, REL: HR 0.58 (0.47-0.72), p < 0.0001, PFS HR 0.52 (0.43-0.64), p < 0.0001, and OS HR 0.46 (0.36-0.60), p < 0.0001. We conducted additional analyses to investigate a possible selection bias in the maintenance group including landmark analysis at 100-days and 6-months post-AHCT2 as well as a subgroup analysis of patients who received melphalan 200mg/m2 as conditioning for AHCT2 (as a surrogate for fitness)- all these analyses also showed improved outcomes in the maintenance group. Second cancers were reported in 17 (5%) patients in the maintenance group and 6 (3%) patients and no-maintenance group (p 0.39). Conclusions: Maintenance therapy after AHCT2 is associated with superior outcomes in MM patients.

BEP Versus BEAM Conditioning for Autologous Hematopoietic Cell Transplantation in Relapsed Lymphoma. A Single Center Retrospective Review of Two Contemporaneous Cohorts

Blood ◽  
2011 ◽  
Vol 118 (21) ◽  
pp. 2019-2019
Author(s):  
Paolo F. Caimi ◽  
Ashley Rosko ◽  
Pingfu Fu ◽  
Huda S. Salman ◽  
Tamila L. Kindwall-Keller ◽  
...  
Keyword(s):  
Serum Creatinine ◽  
Renal Dysfunction ◽  
Cell Transplantation ◽  
Hematopoietic Cell Transplantation ◽  
Conditioning Regimen ◽  
Median Number ◽  
Hematopoietic Cell ◽  
Relapsed Lymphoma ◽  
Autologous Hematopoietic Cell Transplantation

Abstract Abstract 2019 High-dose chemotherapy (HDC) followed by autologous hematopoietic cell transplantation (AHCT) has been shown to result in better outcomes than conventional salvage chemotherapy for treatment of relapsed Hodgkin (Lancet 2002;359:2065–71) and non – Hodgkin lymphoma patients (N Engl J Med 1995;333:1540–5). The relative efficacy of different conditioning regimens is still uncertain. Our center has had extensive experience with BEP, consisting of BCNU (600mg/m2), etoposide (2400mg/m2) and cisplatin (200mg/m2) (Lazarus HM, J Clin Oncol 1992;10:1682–9) with more than 150 patients transplanted using this conditioning regimen. We have observed it to be efficacious and associated with a low incidence of transplant-related mortality (Biol Blood Marrow Transplant 2005;11:13–22). The purpose of this analysis is to compare the outcomes of patients transplanted with BEP with a contemporaneous cohort of patients transplanted with BEAM (BCNU 300mg/m2, etoposide 800mg/m2, cytarabine 1600mg/m2, melphalan 140 mg/m2). We performed a retrospective analysis of 55 consecutive relapsed lymphoma patients who had either BEAM or BEP preparative therapy for AHCT between 2005 and 2010 at our institution. Given the potential for nephrotoxicity and ototoxicity of cisplatin, patients were selected to receive BEAM if they had previous renal dysfunction (any elevation of serum creatinine) or had previous hearing loss. All patients received corticosteroids for prophylaxis of BCNU – induced pneumonitis. The Mann – Whitney test was used for analysis of continuous variables, Fisher's exact test for categorical data, while survival analysis was performed with the Kaplan – Meier method. Twenty-four patients received BEAM and 31 received BEP. The median age was higher in BEAM-treated patients (51 vs. 43 years, p = 0.0392). Other baseline characteristics were comparable between both cohorts: gender (male 54 vs. 58%, p = 0.791); diagnosis (NHL 75 vs. 77.4%, p = 1.000); status of disease at transplant (partial remission or worse 33.3 vs. 35.5%, p = 1.000); median number of previous therapies (2 in both groups, p = 0.51). The rate of non-renal comorbidities was higher in the BEAM cohort, but the difference was not statistically significant (45.8 vs. 32.3%, p = 0.403). The median CD34 cell dose was similar in both groups (6.252 x106 vs. 6.475 x106 CD34 cells/μL, p = 0.842). The rate of complications, including bacteremia, other infections, mucositis, diarrhea and renal dysfunction were not statistically different (Table 1). The small sample size may have prevented us from observing a statistical difference in cardiac toxicity.Table 1.Complications observed after BEAM or BEP conditioning for Autologous Hematopoietic CellBEAM (%)BEP (%)Bacteremia45.835.5p = 0.580Non – bacteremic infections37.541.9p = 0.787Mucositis54.258.1p = 0.791Diarrhea79.164.5p = 0.370Increase in serum creatinine > 50%12.516.1p = 1.000Cardiac complications16.73.2p = 0.153BCNU pneumonitis4.26.4p = 1.000 The median follow up time for the whole cohort was 31 months (28 vs. 34 months, p 0.267). Relapse free survival (RFS) after 36 months was 81.1% and 82.9% for BEAM and BEP, respectively (p = 0.693) (Figure 1). Overall survival at 24 months was 89.6% for BEAM and 90.8% for BEP (p = 0.371) (Figure 2). Among patients transplanted in partial response or worse, the median RFS was 57 months after BEAM and 66 months after BEP (p = 0.3173). There were no deaths in the first 100 days after transplant for both cohorts. There were no differences in the median number of days from hematopoietic cell infusion to discharge (12.5 vs. 12.0 days, p = 0.600) or achievement of ANC >500/μL (10 days for both cohorts, p = 0.415). In conclusion, BEP conditioning achieved comparable engraftment, toxicity and survival outcomes to those achieved by BEAM for treatment of relapsed lymphoma patients. BEP is therefore a valid alternative for treatment of this patient population. The BCNU dose in BEP is twice that in BEAM, but we continue to observe limited rates of BCNU – induced pneumonitis. BEP may be preferable over BEAM in patients with underlying cardiac comorbidity. Longer follow up and prospective trials will help in identifying variables that aid in the selection of patients for the most appropriate conditioning regimen. Disclosures: No relevant conflicts of interest to declare.

Intravenous Busulphan in Combination with ETOPOSIDE and MELPHALAN Used as Conditioning Regimen for Autologous Hematopoietic Cell Transplantation in Lymphomas: Evaluation of Toxicity and Efficacy

Blood ◽  
2010 ◽  
Vol 116 (21) ◽  
pp. 1324-1324
Author(s):  
Despina Mallouri ◽  
Ioanna Sakellari ◽  
Ioannis Batsis ◽  
Varnavas Konstantinou ◽  
Panayotis Baliakas ◽  
...  
Keyword(s):  
Complete Remission ◽  
Blood Cell ◽  
Cell Transplantation ◽  
Red Blood Cell ◽  
Hematopoietic Cell Transplantation ◽  
Conditioning Regimen ◽  
Hematopoietic Cell ◽  
Grade Ii ◽  
Autologous Hematopoietic Cell Transplantation

Abstract Abstract 1324 The standard conditioning regimen used in autologous hematopoietic cell transplantation (autoHCT) for lymphomas is BEAM. During the last year, due to Carmustine (BCNU) unavailability, a new alternative conditioning regimen was designed in our unit consisting of intravenous Busulphan (Busilvex) (3.2mg/kg/day for 3 days), Etoposide (400mg/m̂2/day for 2 days) and Melphalan (140mg/m̂2) (BEM). We retrospectively evaluated the safety and efficacy of the above regimen in 25 patients, aged 30 (16- 65) years, transplanted for Hodgkin (14) and non Hodgkin Lymphomas (DLBCL 7; large B cell mediastinal 1; T-anaplastic 2; MCL 1) between May 2009 and July 2010. The patients received a median of 3 (2- 8) lines of treatment before autoHCT. Disease was chemosensitive to pretransplantation salvage treatment in 17 [6/25 achieved complete remission (24%)], stable in 2 and refractory in 6 patients. According to the Hematopoietic cell transplantation specific comorbidity index, 20 were low (score 0) and 5 intermediate (score 1) risk. Fifteen patients received palifermin and all received cotrimoxazole, antifungal, antiviral and antibiotics as prophylaxis for at least 3 months. The median CD34+ cell dose was 5.59 (2.1- 19.59) ×106̂/Kg and patients received GCSF for a median of 10 (7- 53) days. Prompt engraftment was achieved in 23/25 patients. The median time for neutrophil engraftment (> 500/mm̂3) was day +11 (9- 29), +14 (9- 150) for platelet (>20000/mm̂3) and +11 (8- 43) for erythroid (red blood cell transfusion independency) in 24/25 patients. A second transplantation with double cord blood was offered in one patient because of engraftment failure. In one patient stable engraftment was achieved after a second infusion of autologous cells due to delayed engraftment. The median number of red blood cell transfusions were 3 (0- 15), median single donor platelet units were 4 (0- 36). No red blood cell and no platelet transfusions were required in 4 and 2 patients respectively. Infection (grade II-III) during neutropenia developed in 19 patients (bacteremias mostly; no fungal or respiratory infections). Patients were febrile for a median of 3 (1- 43) days. Twenty-four patients developed mucositis (grade I 6, II 8, III 10) and 21 received parenteral nutrition for 5 (1- 12) days. Nineteen developed liver and gastrointestinal toxicity (elevation of transaminases, nausea/vomiting) grade I- III (grade I 4, grade II 11, grade III 4). The median day of discharge was +15 (10- 32) in 24/25 patients. The patient allografted post autoHCT died at day +63 due to refractory disease and multiple infections. The median follow-up was 7.1 (3-16) months. Eleven patients (44%) were in complete remission (CR) at disease evaluation by CTs one month post autoHCT, without any further treatment. All of them had chemosensitive disease. At last follow up 22 patients are alive and 17 in CR. Three patients succumbed to their disease. The estimated 2-year overall survival (OS) is 90% and disease free survival (DFS) is 60% (95% for patients with chemosensitive disease and 15% for refractory, p<0.05). Despite of the limitations of this study with a small number of patients and short follow up period, the toxicity of the conditioning regimen (BEM) seems to be acceptable and comparable to widely used regimens and offers promising results. For patients with chemosensitive disease BEM seems to be efficacious providing high rates of OS and DFS. Disclosures: No relevant conflicts of interest to declare.

Autologous Hematopoietic Cell Transplantation In Multiple Myeloma Patients Age 70 Years and Older.

Blood ◽  
2010 ◽  
Vol 116 (21) ◽  
pp. 4576-4576
Author(s):  
Qaiser Bashir ◽  
Wei Wei ◽  
Alexandre Chiattone ◽  
Gabriela Rondon ◽  
Simrit Parmar ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Cell Transplantation ◽  
Research Funding ◽  
Hematopoietic Cell Transplantation ◽  
Conditioning Regimen ◽  
Hematopoietic Cell ◽  
High Dose ◽  
Disease Response ◽  
Autologous Hematopoietic Cell Transplantation ◽  
Grade Iii

Abstract Abstract 4576 Introduction: High dose chemotherapy followed by autologous hematopoietic cell transplantation (auto HCT) for multiple myeloma (MM) has shown improved survival compared to conventional chemotherapy. However, the larger clinical trials evaluating the role of auto HCT in MM have included patients who are generally younger than 65 years. Here we report the results of MM patients, age ≥70 years, who received auto HCT at our institution. Methods: We retrospectively analyzed 84 patients, who underwent auto HCT between January 1999 and June 2010 at MDACC. Conditioning regimen was Melphalan 140 mg/m2 (MEL 140) (N=9), 180 mg/m2 (MEL 180) (N=20), and 200 mg/m2 (MEL 200) (N=55). Disease response was assessed at day 100 post transplant. Results: Pertinent patient and disease characteristics are summarized in the Table. Median age at transplant was 72 (70-80) years. Median number of prior treatments was 1 (range: 1–8). Median time from diagnosis to transplant was 8.5 (2.4-151) months. No patient was in CR prior to auto HCT. Median CD34+ cell count and TNC was 4.56 (0.72-11.1) × 106/kg and 10.53 (2.25-57) ×108/kg, respectively. Median follow up is 2 (0.1-7.3) years. Grade III-IV organ toxicity was seen in 35 (51%) patients. Grade III-IV toxicity in patients who received MEL 140, MEL 180, and MEL 200 was 25%, 45%, and 44%, respectively (p value > 0.05). Non-relapse mortality (NRM) at 100 days was 2%. Two patients died in first 100 days. Disease response in evaluable patients (N=79) at day 100 was: CR=15 (19%); VGPR=7 (9%); PR=41 (52%); and SD=10 (13%). Median progression free survival (PFS) and overall survival (OS) from auto HCT was 2.1 years (95% CI 1.78–3.69) and 5.6 years (95% CI 5.51-NA), respectively. 2-year PFS and OS were 56% (95% CI 0.44–0.71) and 80% (95% CI 0.7–0.91), respectively. There was no difference in NRM, PFS, or OS in different MEL groups. Similarly there was no difference in TRM, PFS, and OS in patients ≥ 75 years compared to the patients < 75 years. Conclusion: Auto HCT in myeloma patients age ≥ 70 years is safe and feasible. Toxicity, NRM, response and survival were comparable to younger myeloma patients. The age alone should not be a contraindication 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. Orlowski:Celgene: Consultancy, Research Funding; Millennium Pharmaceuticals, Inc.: Consultancy, 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. Giralt:Celgene: Honoraria, Speakers Bureau; Millenium: Honoraria, Speakers Bureau.

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