Outcomes Following Autologous Stem Cell Transplantation (ASCT) In Patients With Germinal Center B (GCB) and Non-GCB Cell-Like Diffuse Large B Cell Lymphomas (DLBCL) According To Conditioning With BEAM-Rituximab (Standard vs. High-Dose) Vs. BEAM/Yttrium-90 Ibritumomab Tiuxetan (90YIT)

Blood ◽  
2013 ◽  
Vol 122 (21) ◽  
pp. 3350-3350
Author(s):  
Issa F. Khouri ◽  
Rima M. Saliba ◽  
Zijun Y Xu-Monette ◽  
Gabriela Rondon ◽  
Rosamar Valverde ◽  
...  
Keyword(s):  
Stem Cell ◽  
Conditioning Regimen ◽  
High Dose ◽  
Cell Transplant ◽  
Cell Of Origin ◽  
Ibritumomab Tiuxetan ◽  
Bone Marrow Biopsies ◽  
Beta 2 ◽  
Beta 2 Microglobulin ◽  
The Impact

Abstract Background Patients with a DLBCL of GCB immunophenotype have a higher chance of cure than patients with non-GCB DLBCL when treated with conventional chemotherapy. In the relapsed/refractory setting, there are conflicting data regarding the impact of cell-of-origin classification on survival following ASCT. The addition of high-dose rituximab (HDR) (1000 mg /m2 days +1 and +8 after ASCT) has been shown to improve results for patients with relapsed DLBCL who undergo transplantation (Khouri et al, J Clin Oncol 2005;23:2240-7). The optimal rituximab dose to be used with ASCT [HDR vs. standard dose (SDR) 375 mg/m2 days +1 and +8)] has been under investigation at our center. More recently, we and others reported on the safety of incorporating 90YIT (0.4 mCi/Kg) in the conditioning. Herein, we compare outcomes of patients with GCB and non-GCB DLBCL after ASCT according to the conditioning regimen received. Methods and patients 121 de novo DLBCL patients were treated on 4 consecutive trials between 2000 and 2012. We determined the cell-of-origin, based upon the Visco/Young and Choi immunohistochemical algorithms, and classified 64 (53%) as GCB and 57 (47%) as non-GCB tumors. Median age, gender distribution, remission status (CR vs PR), # of prior therapies, IPI, beta-2 microglobulin and LDH distribution were similar in both groups. Patients were staged with CT, PET (whenever indicated) scans and bone marrow biopsies, every 3 months for the first year, every 6 months x 5 years, then yearly thereafter. Patients received BEAM conditioning with either SDR [GCB (n =14), non-GCB (n=7), HDR [GCB (n =31), non-GCB (n=40) or 90YIT[GCB (n =19), non-GCB (n=10)]. Results Determinants for progression (cell-of-origin, age, and gender, and disease status, # of prior therapies, IPI, beta-2 microglobulin and LDH distribution) were studied within each type of conditioning. Within the BEAM-SDR group, the cell-of-origin was the only significant predictor for relapse at 3-years (86% in non-GCB vs. 14% in GCB; P=0.01) (Figure), resulting in improved OS and PFS for the GCB group (both 71% vs 14%, respectively, P=0.06 for OS and 0.04 for PFS). Non-relapse mortality was 0% in this group. Within the BEAM-HDR and BEAM-90YIT groups, GCB and non-GCB patients had a similar rate of relapse (30% vs. 38%, respectively at 3-year, P=0.4) and similar 3-year PFS rates 66% vs 56%, P=0.3), and 3-year OS of 77% vs. 61% (P=0.09). Conclusion Our results suggest similar outcomes for patients with DLBCL of GCB and non-GCB immunophenotype when either HDR or 90YIT is added to the BEAM conditioning. A SDR has been found to be associated with a significantly higher risk of progression and inferior survival in non-GCB patients. Disclosures: Khouri: Spectrum Pharmaceuticals: Consultancy, Research Funding. Off Label Use: Rituximab and ibritumomab tiuxetan for stem cell transplant.

Incorporating Target Immunotherapy into Standard Conditioning Regimen Prior to Autologous Stem Cell Transplantaion (ASCT) Improves the Transplant Outcome for Pateints with Relapsed/Refractroy B Cell Non-Hodgkin Lymphoma (B-NHL).

Blood ◽  
2007 ◽  
Vol 110 (11) ◽  
pp. 1911-1911
Author(s):  
Mohamed I. Farhat ◽  
Reem Karmali ◽  
Stephanie A. Gregory ◽  
Parameswaran Venugopal ◽  
Mohamad Kassar ◽  
...  
Keyword(s):  
Stem Cell ◽  
Disease Progression ◽  
Conditioning Regimen ◽  
Disease Free Survival ◽  
High Dose Chemotherapy ◽  
High Dose ◽  
Cell Transplant ◽  
Free Survival ◽  
The Impact ◽  
Disease Free

Abstract Background: Refractory or relapse B-NHL has a poor prognosis with conventional chemotherapy. Autologous stem cell transplant (ASCT) preceded by high dose chemotherapy has been the preferred therapeutic choice for such patients. The majority of the treatment failures occur within one to two years post transplant with disease progression after transplant accounted for most of the failures. The incorporation of targeted immunotherapy (rituximab) into the upfront and relapse setting is becoming of the standard of care for patients with B-NHL. The objective of this study is to evaluate the impact of rituximab (R) on disease free survival (DFS) when added to a standard conditioning regimen -- BEAM (carmustine, cytarabine, etoposide, and melphalan) prior to ASCT. Methods: A single institution retrospective analysis of 53 patients (pts), whom were heavily pre-treated, underwent ASCT between 08/98 & 07/06. All pts received rituximab in combination with high dose cytoxan for stem cell mobilization. 37 pts received R-BEAM and 16 received BEAM prior to ASCT. Actuarial rate for DFS was estimated from the day of SCT using the Kaplan-Meier method. Results: The group was predominantly men, 73% and 78%, with a median age of 57 years for both the R-BEAM and BEAM group. With a median follow up of 15.7 months, 13/37 (32%) and 11/16 (64%) pts who received R-BEAM and BEAM respectively developed disease progression after ASCT. The 2-yr actuarial disease-free survivals (figure1) were 60% and 21% for the R-BEAM and BEAM arm respectively (p=0.006). Conclusion: In this study, the outcome of pts who received R-BEAM compares favorably to those who receive BEAM alone with significant improvement in disease-free survival. Thus, incorporating target immunotherapy into standard conditioning regimen may have altered the natural history of the disease for pts undergoing ASCT for relapsed/refractory B-NHL. Disease Free survival Disease Free survival

Multicenter Phase II Trial of 90Y-Ibritumomab Tiuxetan with High-Dose Chemotherapy (Busulfan/Cyclophosphamide/Etoposide) Followed by Autologous Stem Cell Transplantation in Relapsed, Refractoried, or High-Risk B-Cell NHL.

Blood ◽  
2007 ◽  
Vol 110 (11) ◽  
pp. 1914-1914
Author(s):  
Byung Woog Kang ◽  
Jae-Cheol Jo ◽  
Shin Kim ◽  
Geundoo Jang ◽  
Sung Sook Lee ◽  
...  
Keyword(s):  
Stem Cell ◽  
High Risk ◽  
Stem Cell Transplantation ◽  
B Cell ◽  
Cell Transplantation ◽  
Autologous Stem Cell Transplantation ◽  
Conditioning Regimen ◽  
High Dose Chemotherapy ◽  
High Dose ◽  
Ibritumomab Tiuxetan

Abstract The need of new effective regimen for high-dose chemotherapy followed by autologous stem cell transplantation (ASCT) in aggressive B-cell non-Hodgkin’s lymphoma (NHL) patients and promising results observed so far in trials with 90Y-Ibritumomab tiuxetan containing regimens in ASCT strongly warrants the investigation of 90Y-Ibritumomab tiuxetan combined busulfan/cyclophosphamide/etoposide (Z-BuCyE) high-dose chemotherapy with ASCT for relapsed, refractoried, or high-risk B-cell NHL. We evaluated efficacy and safety of the combination of Z-BuCyE and ASCT in patients with relapsed, refractoried, or high-risk B-cell NHL. Treatment consisted of two doses of Rituximab (250 mg/m2, IV, day -21, -14) and a single dose of 90Y-Ibritumomab (0.4 mCi/kg, IV, day -14). All patients received conditioning regimen: busulfan (3.2 mg/kg, IV, day -7, -6, -5), etoposide (200 mg/m2, IV, day -5, -4), and cytoxan (50 mg/kg, IV, day -3, -2) followed by ASCT (day 0). Thirteen patients were entered the trial. The median age was 46.1 years (range: 25–60), and 6 (46%) patients were male. Histology was diffuse large B-cell (n=10), follicular (n=1), Burkitt (n=1), and mantle cell lymphoma (n=1). The objective overall response rate (ORR) was 76.9% (10/13): continued CR, 38.5% (5/13); induced CR, 23.1% (3/13); continued or induced PR, 15.4% (2/13). Three patients (23.1%) had a PD after transplantation and two of these patients died of progression. Median follow-up duration was 6.0 months. Median progression-free survival (PFS) and median overall survival (OS) has not yet been reached. Toxicity was principally non-hematologic. Grade 2 toxicity included mucositis (53.8%), nausea (61.5%), vomiting (15.4%), diarrhea (23.1%), and elevation of liver enzyme (7.7%). Grade 3 toxicity included mucositis (15.4%), nausea (23.1%), and diarrhea (23.1%). There was no grade 4 toxicity. Infection occurred in ten patients, bleeding in one patient, and there was no treatment related mortality. This preliminary analysis shows that the combination of Z-BuCyE and ASCT has excellent efficacy and is well-tolerated treatments for relapsed, refractoried or high-risk B-cell NHL. This study will be continued till 20 patients enrollment.

Thalidomide + Dexamethasone as Maintenance after Single Autologous Stem Cell Transplantation Improves Progression-Free Survival (PFS) in Advanced Multiple Myeloma. A Prospective Brazilian Randomized Trial

Blood ◽  
2008 ◽  
Vol 112 (11) ◽  
pp. 3703-3703 ◽  
Author(s):  
Angelo Maiolino ◽  
Vania T. Hungria ◽  
G. Oliveira-Duarte ◽  
LC Oliveira ◽  
DR Mercante ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Stem Cell ◽  
Stem Cell Transplantation ◽  
Disease Progression ◽  
Cell Transplantation ◽  
Autologous Stem Cell Transplantation ◽  
Chromosome 13 ◽  
Beta 2 ◽  
Beta 2 Microglobulin ◽  
The Impact

Abstract Introduction: Autologous stem cell transplantation (ASCT) remains the mainstay of treatment of multiple myeloma (MM) in patients <65 years old. However, most patients relapse after ASCT suggesting that additional treatment is needed. The Brazilian Multiple Myeloma Group designed a study to evaluate the impact of thalidomide maintenance after ASCT. Methods: From October 2003 to July 2008, 212 untreated patients <70 years old were enrolled in a prospective randomized multicenter study. All patients signed an informed consent and the protocol was approved by the Ethical Committees of each center. The treatment consisted of 3 phases: induction with 3–5 cycles of VAD; high-dose cyclophosphamide (4g/m2) plus G-CSF for stem cell mobilization; (3) melphalan 200 mg/m2 and ASCT. On day +60 post ASCT patients were randomized to receive dexamethasone (40 mg/d × 4 days every 28 days) with (arm A) or without (arm B) thalidomide (200 mg daily) for 12 months or until disease progression. Results: The median age was 55 years (27–70), 52% were male, the median serum beta-2 microglobulin was 3.66 mg/dl, 33% were ISS stage 3, 36% were ISS stage 2 and 24% had deletion of chromosome 13. In July of 2008, 93 patients (44%) were randomized: 54 in arm A and 39 in arm B. Reasons for non-randomization were: treatment related deaths during phases 1–3 (n= 39), disease progression (n= 22), ineligible or refused ASCT (n= 7), SMD after ASCT (n= 1), protocol violation (n= 3), abandoned (n= 19), and still in phases 1–3 (n= 28). Clinical characteristics of each group were similar. The median follow-up from diagnosis was 15 months. PFS in arms A and B were 42% (95% confidence interval [CI] 22–62) and 25% (95% CI 5–45), p= 0.07. A multivariate analysis that included baseline serum beta-2-microglobulin and deletion of chromosome 13 showed that maintenance with thalidomide was significantly associated with better PFS (hazard ratio 2.43, 95% CI 1.10–5.35, p=0.03). Overall survival was 65% in arm A (95% CI 35–95) and 74% in arm B (95% CI 44–100), p= NS. Conclusions: A high proportion of MM in Brazil has advanced disease at diagnosis, and this explains the high number of patients who did not reach the maintenance phase. This study shows that the addition of thalidomide to dexamethasone improves PFS after a single ASCT.

Genetic polymorphisms associated with clostridium difficile infection in multiple myeloma patients undergoing autologous stem cell transplantation.

2020 ◽  
Vol 38 (15_suppl) ◽  
pp. 8522-8522
Author(s):  
Issam Hamadeh ◽  
Zainab Shahid ◽  
Manisha Bhutani ◽  
Jai Narendra Patel ◽  
Nury Steuerwald ◽  
...  
Keyword(s):  
Logistic Regression ◽  
Stem Cell ◽  
Antibiotic Prophylaxis ◽  
Conditioning Regimen ◽  
High Dose ◽  
Host Immune System ◽  
Cell Transplant ◽  
Regression Analyses ◽  
Multivariate Logistic Regression ◽  
Buccal Swabs

8522 Background: CDI is the primary cause of infectious diarrhea in immunocompromised patients including those undergoing autologous stem cell transplant (SCT). Given the key role of gut microbiome and its interaction with host immune system, we investigated whether polymorphisms in innate immunity genes (identified through Ingenuity Pathway Analysis) were associated with CDI. Methods: We queried our database to identify MM patients who underwent an autologous SCT between April 2015-June 2019. Patients who had their buccal swabs collected through an IRB approved specimen collection protocol were included herein. Data were collected on age, conditioning regimen, CDI diagnosis, time from admission until CDI diagnosis, absolute neutrophil count (ANC) at time of CDI diagnosis, and antibiotic prophylaxis. Genomic DNA was extracted from buccal swabs and genotyped for 62 single nucleotide polymorphisms (SNPs) in ASPH , RLBP1L1, ATP7B, IL-8, FAK, TNFRSF14, CTH, TLR and IL-4. Univariate and multivariate logistic regression analyses were performed to assess association between CDI and presence of SNPs in these genes. Results: A total of 83 patients were identified (25 cases and 58 controls). Baseline characteristics were comparable between two groups. Median age was 67 years (range: 50-79). All patients received high dose melphalan as conditioning, and the same antibiotic prophylaxis during peri-transplant period. Median time from hospitalization until CDI diagnosis was 10 days (IQR:9 days), and median ANC was 0.7/mL (IQR:1.6/mL). Two SNPs (rs2227307 T > G in IL-8 and rs2234167 G > A in TNFRSF14) were significantly associated with CDI risk in both univariate and multivariate logistic regression analyses (Table). Conclusions: Our findings suggest that rs227307G (in IL-8) and rs2234167A (in TNFRSF14) alleles are potential risk factors for CDI after autologous SCT. Our findings, if validated in a larger cohort, would support genetic testing as a screening tool to identify patients who might benefit from prophylaxis against CDI. [Table: see text]

Single Autologous Stem Cell Transplant Using Busulfan and Cyclophosphamide as Conditioning Regimen in Patients with Multiple Myeloma

Blood ◽  
2008 ◽  
Vol 112 (11) ◽  
pp. 4436-4436
Author(s):  
Giampaolo Talamo ◽  
David F. Claxton ◽  
Joseph Drabick ◽  
David W. Dougherty ◽  
Jeff Sivik ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Stem Cell ◽  
Peripheral Blood ◽  
Single Agent ◽  
Conditioning Regimen ◽  
High Dose ◽  
Cell Transplant ◽  
Transfusion Threshold ◽  
Significant Difference ◽  
High Dose Melphalan

Abstract Autologous peripheral blood stem cell transplantation (ASCT) has been shown to improve survival in patients with multiple myeloma (MM). High-dose melphalan is considered the current standard of care among the preparative regimens used in ASCT for MM patients. We report the results of ASCT in 79 consecutive MM patients using a conditioning regimen with busulfan and cyclophosphamide (Bu/Cy), given as single ASCT and without maintenance therapy. Peripheral blood stem cells were mobilized with cyclophosphamide 5,000 mg/m2 IV + etoposide 1,000 mg/m2 IV, followed by granulocyte colony stimulating factor (G-CSF) 5 mg/Kg/day until the end of stem cell collection. A median of 41.1 × 106 CD34+ cells/Kg (range, 2.1–139.7 × 106) of ideal body weight were mobilized. The conditioning regimen consisted of busulfan 1 mg/Kg PO or 0.8 mg/Kg IV every 6 hours x 16 doses (days -7 to -3), and cyclophosphamide 60 mg/Kg/day IV for 2 days (days -3 to -2). Patients achieved neutrophil engraftment (absolute neutrophil count &gt;500/μL) at a median of +13 days (range, +6 to +21 days), and platelet engraftment (platelets &gt;20,000/μL unsupported by transfusion) at a median of 14 days (range, +11 to +24). Using a transfusion threshold of hemoglobin &lt;8.0 g/dL and platelets &lt;10,000/μL, patients required a median of 2 units of RBC transfusions (range, 0–8), and 1 platelet transfusion (range, 0–15) until hematologic engraftment. Forty-eight and 20 patients reached PR and CR, respectively, for an overall RR of 86%. At a median followup of 41 months (range 2–132 months), the estimated median overall survival (OS) and progression-free survival (PFS) were 45 months [95% confidence interval (CI) = 38–92] and 20 months (95% CI = 15–25), respectively. Veno-occlusive disease developed in 4 pts, and it was lethal in 1 of them. The Bu/Cy regimen was overall well tolerated, and transplant-related mortality was 4%. No statistically significant difference in terms of OS and EFS were observed between the group of patients receiving oral (n=13) vs IV busulfan (n=66). OS was not statistically different between the group receiving ASCT in first remission (n=62) and the group receiving ASCT as salvage therapy, i.e., upon MM progression (n=17), either calculating OS from the day of ASCT or from the day of MM diagnosis. We conclude that our reported clinical outcomes of the Bu/Cy regimen are equivalent to those obtained in historical controls with high-dose melphalan followed by a single ASCT. Thus, given the equivalent effectiveness but greater complexity of administration of the Bu/Cy regimen compared with that of single agent melphalan, we believe the latter should remain the agent of choice for ASCT in MM.

Combination Therapy with BCNU/Etoposide/Melphalan (BEM) as Conditioning Regimen for Autologous Stem Cell Transplant In Multiple Myeloma.

Blood ◽  
2010 ◽  
Vol 116 (21) ◽  
pp. 4587-4587
Author(s):  
Shanshan Liu ◽  
Ann Mohrbacher ◽  
Dan Douer ◽  
Vishesh R Kothary ◽  
Lisa Hanna ◽  
...  
Keyword(s):  
Body Weight ◽  
Stem Cell ◽  
Stem Cell Transplant ◽  
Conditioning Regimen ◽  
Autologous Stem Cell Transplant ◽  
Bone Lesions ◽  
High Dose ◽  
Cell Transplant ◽  
Lytic Bone Lesions

Abstract Abstract 4587 Background: High-dose chemotherapy and autologous stem cell transplant (ASCT) remains an important therapeutic modality for MM patients. Traditionally high-dose single agent melphalan (200 mg/m2; Mel-200) has been used as the conditioning regimen prior to ASCT for MM. We investigated the combination regimen of BCNU, etoposide and melphalan (BEM) in this setting at our center. Methods: All patients who had undergone ASCT for MM utilizing BEM conditioning regimen at Norris Cancer Center, University of Southern California, Los Angeles were eligible. BEM consisted of BCNU 12 mg/kg (actual body weight or ideal body weight whichever was lower) iv on day -5, etoposide 60 mg/Kg iv on day -3, and melphalan 140 mg/m2 iv on day -1, prior to stem cell reinfusion on day 0. Overall survival (OS) was defined as time from MM diagnosis to death, or in patients still alive, the date of last follow-up. Progression-free survival (PFS) was defined as time from ASCT to date of relapse, or in patients without documented relapse, date of death or last follow up, whichever was sooner. Survival for patients with different clinical and disease-specific characteristics was explored using logrank test. Response was assessed according to International Uniform Response Criteria for MM. Results: A total of 44 MM patients underwent ASCT utilizing the BEM conditioning regimen. Of these, evaluable data was available for 42 patients (25 males; 60%, 17 females; 40%) with a median follow up of 27.6 mths. Median age at diagnosis was 54.5 yr (range 34–68) while median time from MM diagnosis to ASCT was 10.5 mths (range 2.8–47.8). MM subtypes included IgA (n=5, 12%), IgG (n=30, 71%) and light chain-only (n=7, 17%). Median bone marrow (BM) plasmacytosis at diagnosis was 42.5% (range 0%-100%). Durie-Salmon (DS) stages included stage I (12%), II (36%) and III (52%), while 4 patients (10%) had renal dysfunction at the time of initial MM diagnosis. Majority of the patients (71%) had lytic bone lesions at the time of diagnosis and 86% (n=36) hade secretory disease. Patients had received a median of 1 prior treatment (range 1–5), while 23 (55%) patients had received novel agents (proteasome inhibitors or IMiDs) prior to the BEM regimen. Response rates prior to and after the regimen are summarized in Table 1. After BEM-ASCT an additional 16 (38%) patients achieved a CR. Median duration of hospitalization and time to engraftment were 19 days (range 15–41) and 10.5 days (range 7–19), respectively. One patient died prior to discharge from the hospital post ASCT (Day 36 post ASCT) for a treatment related mortality of 2%. CR rate post BEM-ASCT was 64% with an ORR of 97%. Relapses have been noted in 25 patients to date. Median OS for all patients was 4.9 yrs (5.6 yrs for patients in CR and 6.6 yrs for patients in PR after BEM-ASCT). Median PFS was 23.9 mths for all patients (25 mths for patients in CR and 21.8 mths for those in PR after BEM-ASCT). No statistically significant differences were noted in OS based on patient gender (p=0.47), age at diagnosis (< or ≥60 yr), MM subtype (p=0.52), DS stage at diagnosis (0.09), patients without lytic bone lesions at diagnosis (p=0.054), secretor status (p=0.2), response status at the time of BEM-ASCT (p=0.9) or prior exposure to novel agents (p=0.62). Conclusions: BEM is a well-tolerated conditioning regimen prior to ASCT in MM and has efficacy comparable to Mel-200. BEM can be effectively employed in patients where Mel-200 is not feasible. We are particularly intrigued by its ability to deliver high CR rates (64%) compared to <30% (historical control). Very encouraging median OS (4.9 yr) and PFS (23.9 mth) rates were noted which were even better in patients who had a measurable response after this regimen. Further investigations will be needed to optimally define its potential as standard conditioning regimen in MM patients undergoing ASCT. Disclosures: No relevant conflicts of interest to declare.

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