Prior Rituximab Reduces Relapse and Improves Survival Following High Dose Chemotherapy and Stem Cell Transplantation for Relapsed Composite Low and Intermediate Grade (Including Transformed) Lymphoma.

Blood ◽  
2006 ◽  
Vol 108 (11) ◽  
pp. 3662-3662
Author(s):  
Khaled M. Ramadan ◽  
Joseph M. Connors ◽  
Abdulwahab J. Al-Tourah ◽  
Randy D. Gascoyne ◽  
Kevin Song ◽  
...  

Abstract The effect of prior exposure to rituximab (ritux) on relapse (REL) and survival following stem cell transplantation (SCT) in patients (pts) with REL composite low and intermediate grade non-Hodgkin lymphoma (L/I-NHL) is unknown. Fifty-four pts with REL L/I-NHL underwent high-dose chemotherapy (CT) and SCT Jan ’89 to June ’05. Follow-up is complete to April ’6 with a median of 32 mo. Ritux was added to CT regimens since 2001 and given at 375 mg/m2. Eighteen pts received ritux at initial diagnosis of NHL or after REL with salvage CT prior to SCT. Pts proceeded to high dose CT with allogeneic (allo) (n=12) or autologous (auto) SCT (n=6). This group was compared with a group of pts not receiving ritux pre-SCT (n=36)(Table 1). Eleven pts (61%) are alive in the ritux group compared with 11 pts (31%) in the non-ritux group. The 2 and 4-y OS for pts who received ritux were 52% and 52%, vs 36% and 24% (p=.12, RR=.52) for pts who did not receive ritux. The EFS were significantly different with 2 and 4-y EFS for the ritux group 56% and 56% vs 24% and 18% (P=.038, RR=.42) for the non-ritux group (figure 1). No effect was seen on TRM. The risk of REL post SCT was significantly lower in the ritux group (p=.017)(figure 2). Two of 18 pts (11%) had NHL REL in the ritux vs 18 of 36 (50%) in the non-ritux group. The hazard rate of REL in pts who received ritux was 20% that of pts in the non-ritux group. Significance maintained in multivariate analysis (p=.016). No impact was seen on graft-versus-host disease (GVHD). Fifty percent and 61% of pts developed acute GVHD grades 2–4 and 50% and 64% of pts developed chronic GVHD in the ritux and non-ritux groups respectively. In conclusion, prior treatment with ritux in pts with relapsed composite L/I-NHL undergoing SCT was associated with reduced risk of REL and improved survival without associated increase in toxicity. Further analysis is underway to clarify the nature of this important finding. Table 1: Clinicopathological characteristics of ritux and non-ritux groups Parameter$ Rituximab group, n=18 (%) Non-rituximab group, n=36 (%) $ all p values are >0.1. *at diagnosis Median age at SCT 48 y 44 y M:F 2.6:1 1.6:1 Allo-SCT 12(67) 28(78) BM involvement* 10(56) 22(61) B symptoms* 7(39) 10(28) Prior purine analogue therapy 8(44) 11(31) Residual disease prior to SCT 9(50) 14(39) TBI in conditioning 13(72) 30(83) Figure Figure Figure Figure

2000 ◽  
Vol 46 (8) ◽  
pp. 1239-1251 ◽  
Author(s):  
Roy D Baynes ◽  
Caroline Hamm ◽  
Roger Dansey ◽  
Jared Klein ◽  
Lucinda Cassells ◽  
...  

Abstract This review focuses on certain of the principles involved in high-dose chemotherapy and radiation therapy along with autologous hematopoietic stem cell transplantation for the treatment of certain malignancies. In addition, the evidence, wherever possible based on randomized data, for the application of this approach in certain malignancies is reviewed. The malignancies highlighted include acute myeloid leukemia, acute lymphoblastic leukemia, non-Hodgkin lymphoma, Hodgkin disease, and breast cancer.


2020 ◽  
Author(s):  
Fatma Keklik Karadağ ◽  
Fahri Şahin ◽  
Güray Saydam

The goal of complete remission (CR) in acute leukemias could be achieved with intensive induction chemotherapy however patients need post remission consolidation strategies such as high-dose chemotherapy, or autologous (ASCT) or allogeneic (allo-SCT) hematopoetic stem cell transplantation for durable response. However, Allo-SCT is getting more attention in last decades because of improvements of conditioning regimens and graft versus host disease (GVHD) prohylaxis strategies and alternatively available donor sources, it is not suitable for all leukemia patients. The patients who would benefit from Allo-SCT or ASCT could be defined more easily by using risk stratification systems and minimal residual disease (MRD) monitoring. ASCT is considered a treatment option even if its use is declining in the world. Herein, we tried to summarize the studies that report the outcomes of ASCT in acute myeloid leukemia (AML) and acute, lymphoblastic leukemia and describe the patients who would be good candidate for ASCT.


Blood ◽  
2006 ◽  
Vol 107 (12) ◽  
pp. 4623-4627 ◽  
Author(s):  
Douglas A. Stewart ◽  
Nizar Bahlis ◽  
Karen Valentine ◽  
Alex Balogh ◽  
Lynn Savoie ◽  
...  

AbstractA single center, prospective clinical trial was conducted evaluating 2 cycles of induction high-dose chemotherapy for adults younger than 65 years of age with aggressive non-Hodgkin lymphoma (NHL) and 2 to 3 Age-Adjusted International Prognostic Index risk factors. Patients received one cycle of standard dose cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP) followed by one cycle of dose-intensive cyclophosphamide 5.25 g/m2, etoposide 1.05 g/m2, cisplatin 105 mg/m2 (DICEP), then underwent autologous blood stem cell collection, followed by one cycle of high-dose carmustine (BCNU) 300 mg/m2, etoposide 800 mg/m2, Ara-C 1600 mg/m2, melphalan 140 mg/m2 (BEAM), and autologous stem cell transplantation (ASCT) and radiotherapy to prior bulk. From June 1998 to August 2004, 55 patients aged 20 to 63 years (median 44 years) were accrued, 51 (92%) of whom had diffuse large B-cell NHL. Poor prognostic factors included stage 4 (n = 46), elevated lactate dehydrogenase (LDH; n = 47), Eastern Cooperative Oncology Group (ECOG) performance status 2 to 4 (n = 43), bulky mass more than 10 cm (n = 34), and marrow involvement (n = 16). Only one patient experienced nonrelapse mortality. With a median follow-up of 49 months, 4-year event-free survival (EFS) and overall survival (OS) rates for all 55 patients are 72% (95% confidence interval [CI] = 60%-84%) and 79% (95% CI = 69%-90%), respectively. In conclusion, CHOP-DICEP-BEAM is feasible and gave encouraging EFS and OS for patients with poor-prognosis aggressive NHL.


Blood ◽  
2014 ◽  
Vol 124 (21) ◽  
pp. 3986-3986
Author(s):  
Justin Hasenkamp ◽  
Georg Hess ◽  
Bernd Hertenstein ◽  
Mathias Witzens-Harig ◽  
Lutz Uharek ◽  
...  

Abstract Background: Patients with aggressive B cell Non-Hodgkin-Lymphoma failing from immune-chemotherapy show disappointing results with standard salvage therapies and consolidation of high-dose chemotherapy with autologous stem cell transplantation. Especially in cases never in remission or with early relapse outcome is poor. Several groups started trials combining high-dose chemotherapy of carmustin, etoposide, cytarabine and melphalan (BEAM) with 90Yttrium ibritumomab tiuxetan to enhance the efficacy of the preparative regimen. In this trial we tested safety, feasibility and studied efficacy of reduced intervals of 90Yttrium ibritumomab tiuxetan to autologous stem cell transplantation after BEAM. Methods: Patients without disease progression during salvage therapy of relapsed or refractory CD20+ aggressive B-NHL were included in this prospective, multicenter, phase I/II trial. Primary endpoint was the minimum tolerable interval of 90Yttrium ibritumomab tiuxetan given as close as possible to ASCT defined as <2 patients with dose limiting toxicity in a 6+6 patient cohort. We reduced the time interval of standard dose 90Yttrium ibritumomab tiuxetan (0.4 mCi/kg body weight) to ASCT after BEAM from 14 to 12 and finally 10 days to foster the disease control by more concomitant radioimmunotherapy and high-dose chemotherapy. Results: From 2006 to 2009 42 patients were screened for inclusion. Reasons for screening failure were progressive disease during salvage therapy (n=8), death (n=2), not aggressive B-NHL (n=2), impaired organ function (n=2), and other (n=2). Median age of the 26 patients enrolled was 58 years (34-66). 12 patients were allocated to cohort 1 (interval 14 days), 6 patients to cohort 2 (interval 12 days) and 8 patients to cohort 3 (interval 10 days). Histology included 14 DLBCL, 6 FL III°, 5 transformed FL and 1 aggressive B-NHL without further subtyping. 11 from 26 patients had primary refractory disease or early relapse within 12 months after diagnosis. Secondary IPI was >1 in 14 patients. Response to salvage therapy was CR in 6/26 patients and PR in 12/26 patients. 20/26 patients achieved CR after study treatment. Two early deaths (d +7, +18) occurred due to infections. All patients receiving stem cells engrafted with median recovery of leukocytes and platelets at d+10 and +13, respectively. We observed no correlation of toxicities and the study cohorts with the different intervals. At median follow-up of the survivors of 3.5 years the overall survival is 76%, the progression free survival is 67% and time to progression 26%. Lymphoma was the main cause of death. Stratified to time intervals of 90Yttrium ibritumomab tiuxetan and autologous stem cell transplantation revealed time to progression of 50% with 90Yttrium ibritumomab tiuxetan at d-14, 16% at d-12 and 0% at d-10. Conclusions: 90Yttrium ibritumomab tiuxetan and BEAM followed by autologous stem cell transplantation was safe and feasible. The minimum tolerable interval of 90Yttrium ibritumomab tiuxetan and autologous stem cell transplantation is 10 days. With shorter intervals of radioimmunotherapy and high-dose chemotherapy and therefore more concomitant therapy, we did not observed excessive toxicity, but enhanced disease control of refractory or relapsed aggressive B-NHL. Our results compare favorable to standard BEAM or allogeneic stem cell transplantation. A formal comparison in a phase III trial is warranted. Disclosures Off Label Use: 90Yttrium ibritumomab tiuxetan (Zevalin(R)), radioimmunotherapy of CD20+ lymphoma.


2001 ◽  
Vol 28 (4) ◽  
pp. 377-388 ◽  
Author(s):  
Roy D. Baynes ◽  
Roger D. Dansey ◽  
Jared L. Klein ◽  
Caroline Hamm ◽  
Mark Campbell ◽  
...  

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