BEAM or BeEAM High-Dose Chemotherapy Followed By ASCT: A Single Center Comparative Analysis of Toxicity

Blood ◽  
2016 ◽  
Vol 128 (22) ◽  
pp. 4648-4648
Author(s):  
Vincent Ribrag ◽  
Khalil Saleh ◽  
Alina Danu ◽  
Serge Koscielny ◽  
Sylvain Pilorge ◽  
...  
Keyword(s):  
Board Of Directors ◽  
Median Time ◽  
Hodgkin’S Lymphoma ◽  
Conditioning Regimen ◽  
Median Number ◽  
High Dose Chemotherapy ◽  
Case Control ◽  
Hodgkin's Lymphoma ◽  
High Dose ◽  
Advisory Committees

Abstract Introduction: The BEAM (carmustine (BCNU), etoposide, aracytin and melphalan) standard conditioning regimen in autologous stem-cell transplantation is widely used since 1990 in patients with relapsed/refractory non Hodgkin's lymphoma (NHL) and Hodgkin's lymphoma (HL) who remain sensitive to salvage therapy. Recently, a phase Ib-II feasibility study using bendamustine rather than BCNU in the same indication was reported, but was not really compared to BEAM concerning safety. We report herein a safety analysis of Bendamustine-EAM (BeEAM) with a control BEAM counterpart paired cohort (2/1). Methods: We performed a case control retrospective study of patients with NHL and HL who underwent high-dose chemotherapy (HDC) with BeEAM regimen between January 2015 and December 2015. We matched each BeEAM patient with two patients having the same age, sex and number of treatment lines who underwent BEAM and ASCT between January 2008 and December 2014. No patient presented significant comorbidity. The BEAM regimen consisted in BCNU on day -6 (300mg/m2) cytarabine daily from day -6 to day -3 (200mg/m2 every 12 hours), etoposide daily from day -6 to day -3 (100mg/m2 every 12 hours) and melphalan on day -2 (140mg/m2). A similar scheme was adopted in BeEAM arm with bendamustine on day -6 and -5 (100mg/m2/d) replacing BCNU. Autologous stem cells were reinfused on day 0. Unfractionated heparin was used with Bendamustine to prevent veno-occlusive disease. Pegfilgrastim 6mg was injected subcutaneously on day 4. Febrile neutropenia was treated according to ESMO guidelines. Results: One hundred and two patients (68 BEAM and 34 BeEAM) were analyzed. Median age was 48 years in both arms. 61.8% of patients were male and 38.2% female. A median number of 4.4 x106 CD34 were reinfused in the two groups. The median time to neutrophils recovery (> 0.5 x109) was similar between the two arms (9.06 vs 8.86 days, p=0.3). Grade 3 or greater diarrhea according to Commun Terminology Criteria for Adverse Events (CTCAE v4.03) classification was significantly more frequent in BeEAM patients (44 vs 13.2%, p=0.001). Median time to hospital discharge was significantly longer in BeEAM group (23 vs 20.8 days, p=0.0047). The median loss of weight during hospitalization was significantly greater in BeEAM patients (3.3 vs 1.9 kg, p=0.014). The median number of days with fever >38°C and with intravenous antibiotics was significantly higher in BeEAM group (6.06 vs 3.38, p<0.001; 10.76 vs 8.22, p=0.0012 respectively). Five patients in BeEAM arm (14.7%) and 3 patients in BEAM (4.4%) developed grade 2-3 liver cytolysis. Four patients in BeEAM arm developed grade 1 renal toxicity. Six patients presented bacteremia (17.6%) in BeEAM versus 8 patients (11.7%) in BEAM arm. Incidence of mucositis, nausea and vomiting was similar between the two groups. Four patients in the BeEAM arm were rehospitalized for recurrent fever three to five days after discharge. No death occurred in both groups during the ASCT procedure. Conclusion: Our results based on retrospective case-control study suggest that BeEAM conditioning regimen followed by ASCT seems to be more toxic than the standard BEAM regimen. Disclosures Ribrag: gilead: Membership on an entity's Board of Directors or advisory committees; infinity: Membership on an entity's Board of Directors or advisory committees; nanostring: Membership on an entity's Board of Directors or advisory committees; pharmamar: Membership on an entity's Board of Directors or advisory committees; nanostring: Membership on an entity's Board of Directors or advisory committees; ESAI: Membership on an entity's Board of Directors or advisory committees; incyte: Membership on an entity's Board of Directors or advisory committees; incyte: Membership on an entity's Board of Directors or advisory committees; BMS: Membership on an entity's Board of Directors or advisory committees; ESAI: Membership on an entity's Board of Directors or advisory committees; BMS: Membership on an entity's Board of Directors or advisory committees; servier: Consultancy; argenX: Research Funding. Michot:Bristol-Myers Squibb: Membership on an entity's Board of Directors or advisory committees.

scholarly journals A Phase 2 Trial of Ibrutinib and Nivolumab in Patients with Relapsed or Refractory Classical Hodgkin's Lymphoma

Blood ◽  
2020 ◽  
Vol 136 (Supplement 1) ◽  
pp. 29-29
Author(s):  
Walter Hanel ◽  
Beth A. Christian ◽  
Kami J. Maddocks ◽  
Narendranath Epperla ◽  
Basem M. William ◽  
...  
Keyword(s):  
Board Of Directors ◽  
Median Time ◽  
Research Funding ◽  
Response Rate ◽  
Immune Escape ◽  
Chronic Gvhd ◽  
Complete Response ◽  
Median Number ◽  
Hodgkin's Lymphoma ◽  
Advisory Committees

Introduction: Classical Hodgkin's Lymphoma (cHL) is characterized by an extensive inflammatory infiltrate with abundant Th2 and Treg cells which facilitate immune escape of Reed Sternberg (RS) cells and provides a growth promoting microenvironment by cytokine secretion and CD40/CD40L engagement. Our group previously show that ibrutinib irreversibly inhibits both Bruton's tyrosine kinase (BTK) and interleukin-2 inducible kinase (ITK), a kinase important in Th2 signaling (Dubovsky et al Blood 2013). We hypothesized that the addition of ibrutinib to nivolumab would lead to deeper and more durable responses in cHL by normalizing the Th1/Th2 balance thus reversing immune escape of RS cells. We present results of a planned interim analysis of the first 10 patients enrolled with a data cutoff of June of 2020. Methods: This is a single arm, phase II, single institutional clinical trial testing the clinical activity of nivolumab in combination with ibrutinib in patients ≥18 years of age with histologically confirmed cHL who have received at least one prior line of therapy and who were either not candidates for or had a prior autologous stem cell transplant (ASCT). Prior treatment with nivolumab was allowed. Ibrutinib was administered at 560 mg daily until progression in combination with nivolumab 3 mg/kg IV every 3 weeks for 16 cycles. The primary objective was complete response rate (CRR) prior to cycle 7 assessed per Lugano criteria. Adverse events (AEs) were reported using CTCAE Version 4.0. Results: Of the first 11 cHL patients enrolled, one patient withdrew consent prior to initiating therapy. Of the remaining 10 patients, the median age was 41 years (range 20-84) and 4 patients (40%) were male. The median number of prior lines of treatment was 4.5 (range 1-11), 5 patients (50%) had prior ASCT, 8 patients (80%) had prior brentuximab, and 5 patients (50%) had prior nivolumab. Four of the five patients with prior nivolumab had progressed while receiving therapy while the remaining patient had stable disease upon completing nivolumab with a median time from the last nivolumab treatment of 15.6 months (range 0.7-23.2). Of the 10 patients who received treatment, one patient came off study after two cycles due to persistent grade 2 transaminitis lasting for several weeks attributed to nivolumab requiring high dose oral steroids. One patient came off study after cycle 9 due to grade 3 hematuria attributed to ibrutinib and another came off study due to a pericardial effusion after 8 cycles of ibrutinib maintenance. In the remaining patients, treatment was generally well tolerated with most AEs being grade 1-2 (Table 1). The median number of total cycles received was 9 (range 2-22). Of the 9 patients evaluable for response, 6 patients responded (ORR = 66%), 4 of whom had a complete response (CRR = 44%) with a median time to response of 2 months (Table 2, Fig.1). In intention-to-treat analysis, the ORR was 60% and CRR was 40% meeting our prespecified interim efficacy endpoint of a 30% CRR for trial continuation. Notably, of the 5 patients with prior nivolumab, 3 responded to nivolumab + ibrutinib (ORR = 60%), with one having a CR (CRR = 20%). Overall, at a median follow up of 9.5 months, both the median PFS and duration of response have not yet been reached, with 3 patients remaining in CR at the time of data cutoff. Three of 4 patients discontinued trial treatment to undergo SCT [2 allogeneic; 1 autologous]. Of the 2 allogeneic SCT patients, the first one underwent SCT 3 weeks after the last nivolumab infusion and developed multi-organ acute graft-versus-host disease (GVHD) followed by severe chronic GVHD requiring extracorporeal photopheresis. The second patient underwent allogeneic SCT 2 months following the last nivolumab infusion and had no acute GVHD and experienced only mild chronic GVHD which was medically managed. Conclusions: Although the numbers are small and further recruitment is ongoing (target n=17), the combination of ibrutinib and nivolumab was generally well tolerated and with high response rate with more than half of responding patients achieving a CR. In addition, responses were seen in patients with prior nivolumab treatment. Our results suggest a possible novel role for BTK inhibition in reversing nivolumab resistance in cHL, at least in some cases. Correlative studies including peripheral blood and tumor immune subset analyses are ongoing and the latest results will be presented at the meeting. Disclosures Christian: Acerta: Research Funding; Celgene: Research Funding; Genentech: Research Funding; Merck: Research Funding; Millenium: Research Funding; MorphoSys: Research Funding; F Hoffman-La Roche: Research Funding; Triphase: Research Funding; Seattle Genetics: Membership on an entity's Board of Directors or advisory committees, Research Funding; Verastem: Membership on an entity's Board of Directors or advisory committees; AstraZenica: Membership on an entity's Board of Directors or advisory committees. Maddocks:Morphosys: Consultancy, Honoraria; Celgene: Consultancy, Honoraria; Seattle Genetics: Consultancy, Honoraria; Karyopharm: Consultancy; ADC Therapeutics, AstraZeneca: Consultancy; BMS: Consultancy, Research Funding; Pharmacyclics: Consultancy, Honoraria. Epperla:Verastem Oncology: Speakers Bureau; Pharmacyclics: Honoraria. William:Incyte: Research Funding; Dova: Research Funding; Celgene: Consultancy, Honoraria; Seattle Genetics: Research Funding; Merck: Research Funding; Kyowa Kirin: Consultancy, Honoraria; Guidepoint Global: Consultancy. Jaglowski:Novartis: Consultancy, Research Funding; CRISPR: Consultancy; Kite, a Gilead Company: Consultancy, Research Funding; Juno: Consultancy. Bond:Seattle Genetics: Honoraria. Brammer:Celgene Corporation: Research Funding; Seattle Genetics, Inc.: Speakers Bureau. Baiocchi:viracta: Consultancy, Membership on an entity's Board of Directors or advisory committees; Prelude Therapeutics: Consultancy, Research Funding. OffLabel Disclosure: This trial uses ibrutnib in cHL to augment the responses of concurrent nivolumab administration.

Intravenous (i.v.) Busulfan (Bu) Plus Melphalan (Mel) Is a Well-Tolerated Preparative Regimen for Stem Cell Transplantation (SCT) in Patients (pts) with Advanced Lymphoid Malignancies.

Blood ◽  
2005 ◽  
Vol 106 (11) ◽  
pp. 2742-2742
Author(s):  
Partow Kebriaei ◽  
Timothy Madden ◽  
Neil Thapar ◽  
Elizabeth J. Shpall ◽  
Chitra Hosing ◽  
...  
Keyword(s):  
Median Time ◽  
Conditioning Regimen ◽  
Test Dose ◽  
Median Number ◽  
High Dose Chemotherapy ◽  
Fixed Dose ◽  
High Dose ◽  
Lymphoid Malignancies ◽  
Grade Ii ◽  
Grade Iii

Abstract High dose chemotherapy and SCT is an accepted treatment option for pts with relapsed lymphoid malignancies. However, relapse remains a significant issue for pts with advanced disease. A double alkylating regimen of Bu and Mel has been suggested as an effective and myeloablative pre-transplant conditioning regimen. Historically, oral Bu was used and the combination resulted in considerable mucositis and VOD. Recently, an i.v. formulation of Bu has been developed that has less pharmacokinetic (PK) variability. We are investigating the safety and efficacy of i.v. Bu-Mel in pts with lymphoid malignancies undergoing auto- or allo-SCT. Patients and Methods: The conditioning regimen consists of i.v. Bu 130 mg/m2 over 3 hr daily for 4 days, either as a fixed dose per BSA, or to target an average daily AUC of 5,000 μMol-min ± 12% determined by a test dose of i.v. Bu at 32 mg/m2 given 48 hours prior to the high dose regimen. After the four daily Bu doses, there is a rest day, followed by two daily doses of Mel at 70mg/m2. Stem cells are infused the following day. Dilantin is administered for seizure prophylaxis. GVHD prophylaxis consists of tacrolimus and mini-dose methotrexate for pts receiving allo-SCT. Results: 14 pts (10 M/4 F) with median age 32 years (range 20–65) have been enrolled to date: MM (n=3), NHL (n=3), HD (n=8). The median number of prior chemotherapy regimens was 3 (range 2–8). At time of study entry, 2 pts were in CR2, 5 were in first relapse, and 7 had primary- or relapsed refractory disease. The median CD34+ cell dose infused was 4.88 x 106/kg (range 2.3–7.7). Median time to ANC ≥ 0.5 x 109/L was 9 days for auto-SCT pts (n=11), and 14 days for allo-SCT pts (n=3). Median time to platelet count ≥ 20 x 109/L was 9 days for auto-SCT pts, and 14.5 days for allo-SCT pts. All allo-SCT pts had 100% donor chimerism by day 30. 11 pts had i.v. Bu delivered per test dose guidance; 3 pts received fixed dose Bu at 130 mg/m2. The median daily systemic Bu exposure was 5292 μMol-min (range 4113–6734) in the dose-adjusted population. Median Bu clearance was slightly lower than reported in other studies at 99 ml/min/m2 (range 69–116). 7 of 11 pts were within ± 12% of the exposure target; 3 pts had AUCs above 6,000 μMol-min per dose. 3 of 11 evaluable pts have achieved complete remissions and 5 a partial response. With follow-up time of 7 to 117 days, there has been 1 death from disease progression (day 117). Grade II-IV acute GVHD was noted in 2 of 3 allo-SCT pts. The treatment was well tolerated, with grade I or II mucositis as the most common regimen-related toxicity. 2 auto-SCT pts developed grade III toxicity (mucositis and gastritis), and 1 allo-SCT pt developed grade III reversible acute renal failure. Grade II reversible hyperbilirubinemia was noted in 1 allo-SCT pt. No grade IV toxicity has been observed. Conclusion: Intravenous Bu-Mel is well tolerated with prompt neutrophil and platelet engraftment. Individualized PK-directed dosing of i.v. Bu is feasible, and likely contributes to the low toxicity profile of this regimen. It is too early to assess efficacy.

scholarly journals Benda-BEAM High-Dose Therapy Prior to Auto-SCT Is Effective in Resistant/Relapsed DLBCL

Blood ◽  
2015 ◽  
Vol 126 (23) ◽  
pp. 1999-1999 ◽  
Author(s):  
Alessandro Isidori ◽  
Stefano Guidi ◽  
Potito Rosario Scalzulli ◽  
Attilio Olivieri ◽  
Emanuele Angelucci ◽  
...  
Keyword(s):  
Clinical Trials ◽  
Board Of Directors ◽  
Hodgkin Lymphoma ◽  
Median Time ◽  
Real World ◽  
Median Number ◽  
High Dose ◽  
High Dose Therapy ◽  
Advisory Committees ◽  
Non Hodgkin Lymphoma

Abstract Background: The most important drawback of clinical trials of high-dose therapy (HDT) followed by autologous stem cell transplant (ASCT) in lymphomas is the high heterogeneity of histological entities. Therefore, the statistical power is reduced, and data are not conclusive. We previously demonstrated the safety of a new conditioning regimen with bendamustine, etoposide, cytarabine, and melphalan (BeEAM) prior to ASCT in resistant/relapsed lymphoma patients. This combination of drugs was able to induce a high CR rate in a population that did not have an opportunity of being cured with other therapies. However, that study enrolled both Hodgkin and non-Hodgkin lymphoma patients. Aims: We designed a phase II study to evaluate the efficacy of the BeEAM conditioning in resistant/relapsed diffuse large B-cell non-Hodgkin lymphoma (DLBCL) patients. Patients and methods: The study was registered at European Union Drug Regulating Authorities Clinical Trials (EudraCT) N. 2011-001246-14. Until now, 61 patients (median age 54 years, range 19-69) with resistant/relapsed DLBCL were enrolled. The primary end-point of the study is to evaluate the 1-year complete remission rate. Results: Briefly, 46/61 patients had advanced stage disease (III-IV); 20 were primary refractory and 41 had relapsed after a median number of 2 lines of therapy (range: 1-3). Twenty-one patients had 1 or more relevant comorbidities (range: 1- 5). 30 patients were in II or subsequent CR after salvage therapy, whereas 27 were in PR and 4 had stable or progressive disease. A median number of 5.72x106 CD34+/kg cells (range 2.21-10.60) collected from peripheral blood was reinfused to patients. All patients engrafted, with a median time to ANC>0.5x109/l of 10 days. Median times to achieve a platelet count >20x109/l and >50x109/l were 12 and 17 days respectively. Twenty-two out of 61 patients presented a fever of unknown origin (36%), whereas 24 patients (39%) presented a clinically documented infection. All patients received G-CSF after transplant for a median time of 8 days (range: 8-13). One patient died due to an incomplete hematological recovery after transplant, producing an overall transplant related mortality of 2.7%. Fifty-seven patients are evaluable for response: 48/57 (84%) obtained a CR, 3/57 (5%) a PR, whereas 6/57 (11%) did not respond to therapy. After a median follow-up of 10.5 months after transplant (range 3-37), 6/57 (11%) patients were refractory, 12/57 (21%) relapsed and 39/57 (68%) are still alive, in continuous CR. Conclusion: Our clinical trial was designed to closely resemble real-world treatment for these patients. During the study, we transplanted a similar proportion of the patients that would have received ASCT in a real-world scenario. While we cannot make sound comparisons without head-to-head trials, results from previous studies using HDT regimens in DLCBL have not been as encouraging as ours. Accordingly, our data preliminary provide the evidence that the Benda-BEAM regimen is safe and has promising high efficacy in resistant-relapsed aggressive DLBCL patients. Acknowledgments: The study was supported in part by AIL Pesaro Onlus. Mundipharma Italy is grateful acknowledged for providing Bendamustine free of charge. Disclosures Patriarca: Janssen-Cilag, Celgene, Merck Sharp & Dohme: Honoraria. Zinzani:Gilead: Membership on an entity's Board of Directors or advisory committees; Takeda: Membership on an entity's Board of Directors or advisory committees; Celgene: Membership on an entity's Board of Directors or advisory committees; J&J: Membership on an entity's Board of Directors or advisory committees; Pfizer: Membership on an entity's Board of Directors or advisory committees.

High-Dose Chemotherapy and Autologous Hematopoietic Progenitor Cell Transplantation (AHCT) for Non-Hodgkin’s Lymphoma (NHL) in Patients over 65 Years of Age.

Blood ◽  
2006 ◽  
Vol 108 (11) ◽  
pp. 3059-3059
Author(s):  
Chitra Hosing ◽  
Rima M. Saliba ◽  
Grace-Julia Okoroji ◽  
Uday Popat ◽  
Daniel Couriel ◽  
...  
Keyword(s):  
Median Time ◽  
Univariate Analysis ◽  
Conditioning Regimen ◽  
Disease Status ◽  
Median Number ◽  
High Dose Chemotherapy ◽  
Hematopoietic Progenitor Cell ◽  
High Dose ◽  
Entire Cohort ◽  
Grade 3

Abstract High-dose chemotherapy followed by AHCT is the treatment of choice for relapsed NHL. Often this therapy is not offered to patients over 65 yrs of age because of concerns regarding their ability to tolerate “aggressive therapy”. We present a retrospective analysis of 99 consecutive pts. who underwent AHCT for NHL at our institution from 6/96–3/06. RESULTS: Median age at AHCT was 68 yrs (range, 65–83). Seventy percent were males. Most common histologies were DLCL (55%), MCL (15%), and FL grades 1–3 (15%). Median number of chemoregimens administered prior to AHCT were 2 (range, 1–6). Median IPI score at AHCT was 1 (range, 0–4). Majority of patients (99%) had a ECOG PS score of < 2 prior to AHCT. Forty-four percent pts were in CR/CRu, 45% were in PR, and 11% had PD/SD. The preparative regimen comprised of BEAM (35%), BEAM/rituximab (53%), and Cy/TBI +/− rituximab (10%). Median hospital stay was 23 days (range, 6–85) for AHCT with 38% requiring readmission within the first 100 days. Source of progenitor cells was HPC-A in 89%. Median CD34+ cell dose infused/kg was 4.4 x 106 (0.1–32.2). All patients engrafted. Median time to reach ANC ≥ 500/mm3 was 10 days (range 7–47). Ten patients never achieved a platelet (PLT) count of 20,000/mm3. For the remaining 88 pts., median time to reach PLT ≥ 20,000/mm3 was 13 days (range, 6–375). Median number of PRBC units transfused were 4 (range, 0–50) and median number of PLT transfusions required were 4 (range, 0–35). Grade 3–5 RRT toxicity is summarized in Table. Table *RRT Grades 3–5 Age years (No.) 65–69 (58 pts) 70–75 (34 pts) > 75 (8 pts) *CTCAE ver 3.0 Toxicity Grade 3/4/5 3/4/5 3/4/5 Pulmonary (pnemonitis) 1/1/0 0/0/1 0/0/1 GI (diarrhea) 6/0/0 2/0/0 0/0/0 GI (mucositis/stomatitis) 6/0/0 0/0/0 1/0/0 GI (nausea) 0/0/0 0/0/0 1/0/0 Neurologic (confusion) 1/0/0 1/0/0 0/0/0 GU (inc creatinine) 1/0/0 2/0/0 0/0/0 Hepatic 1/1/0 1/0/0 0/0/0 Cardiovascular 3/0/0 1/0/0 1/1/0 Allergy (BCNU) 1/0/0 0/0/0 0/0/0 Skin rash 1/0/0 0/0/0 0/0/0 Fatigue/Bone pain 1/0/0 0/0/0 1/0/0 Cumulative TRM was 12 % (95% CI 6–22) at 3 yrs. Median follow-up among survivors is 26 mths (range, 1–115). OS at 3 yrs was 61% (95% CI 49–71) for the entire cohort. At 3 yrs the DFS was 48% (95% CI 33–61), 68% (95% CI 36–87), and 63% (95% CI 22–87) for DLCL, MCL and FL respectively. On univariate analysis IPI > 1, LDH > normal, and SD/PD at the time of AHCT were predictors of worse OS. Disease status at transplant and LDH > normal remained significant predictors for OS on multivariate analysis. Age, gender, histology, number of prior chemoregimens, time from diagnosis to AHCT, and conditioning regimen were not significant predictors of OS. Cause of death was disease progression/relapse in 60%. Eight patients developed sMDS/AML after AHCT. CONCLUSIONS: Patients over 65 yrs of age can undergo AHCT with acceptable toxicity and should be considered transplant candidates if they have chemosensitive disease and an IPI score of ≤ 1 at the time of AHCT.

scholarly journals High-dose chemotherapy and auto-SCT in elderly patients with Hodgkin's lymphoma

2011 ◽  
Vol 46 (10) ◽  
pp. 1339-1344 ◽  
Author(s):  
N Puig ◽  
M Pintilie ◽  
T Seshadri ◽  
K al-Farsi ◽  
N Franke ◽  
...  
Keyword(s):  
Elderly Patients ◽  
Hodgkin’S Lymphoma ◽  
High Dose Chemotherapy ◽  
Hodgkin's Lymphoma ◽  
High Dose

scholarly journals Curability of relapsed childhood B-cell non-Hodgkin's lymphoma after intensive first line therapy: a report from the Societe Francaise d'Oncologie Pediatrique

Blood ◽  
1993 ◽  
Vol 81 (8) ◽  
pp. 2003-2006 ◽  
Author(s):  
T Philip ◽  
O Hartmann ◽  
R Pinkerton ◽  
JM Zucker ◽  
JC Gentet ◽  
...  
Keyword(s):  
B Cell ◽  
Hodgkin’S Lymphoma ◽  
High Dose Chemotherapy ◽  
Marrow Transplant ◽  
Hodgkin's Lymphoma ◽  
High Dose ◽  
First Line Therapy ◽  
Line Therapy ◽  
Non Hodgkin’S Lymphoma ◽  
Non Hodgkin's Lymphoma

Abstract The very high cure rate in advanced B-cell non-Hodgkin's lymphoma in children using intensive multiagent therapy has been previously reported by the French Societe Francaise d'Oncologie Pediatrique lymphoma Malin B type (LMB) group. To address the issue of salvageability in an unselected group of patients who had all received the same front-line therapy, the outcome of relapses following the LMB 84 (216 patients) protocol have been reviewed. Fourteen percent of patients achieving complete remission (CR) relapsed, ie, 27 of 195. Relapse sites comprised the central nervous system (CNS) alone (6 cases), lung or mediastinum (2 cases), abdomen (8 cases), head and neck (2 cases), or multifocal (9 cases). There were three early deaths due to disease. Twenty-four patients received rescue chemotherapy regimens and 15 were treated with high-dose chemotherapy and bone marrow rescue (1 allogeneic). Of these, 9 were in second CR, 4 in second partial remission, and 2 treated during progressive disease. One died in CR from treatment-related toxicity. Ten relapsed postbone marrow transplant and 4 are alive disease free and probably cured. Two of the long-term survivors had some delay during initial chemotherapy due to toxicity and two were isolated CNS relapses. Twelve of 27 patients did not proceed to megatherapy (12 of 12 died).

High-dose chemotherapy and peripheral hematopoietic stem cell transplantation in relapsed/refractory Hodgkin’s lymphoma

2018 ◽  
Vol 104 (6) ◽  
pp. 471-475 ◽  
Author(s):  
Mouhammed Kelta ◽  
Jamal Zekri ◽  
Ehab Abdelghany ◽  
Jalil Ur Rehman ◽  
Zahid Amin Khan ◽  
...  
Keyword(s):  
Stem Cell ◽  
Stem Cell Transplantation ◽  
Cell Transplantation ◽  
Hodgkin’S Lymphoma ◽  
High Dose Chemotherapy ◽  
Salvage Chemotherapy ◽  
Hodgkin's Lymphoma ◽  
Phase Iii ◽  
High Dose

Purpose: High-dose chemotherapy (HDCT) and autologous stem cell transplantation (ASCT) is used to treat patients with relapsed Hodgkin’s lymphoma. In this retrospective study we report our experience with patients who underwent HDCT and ASCT. Methods: All patients ≥15 years old with relapsed/refractory Hodgkin’s lymphoma who underwent HDCT and ASCT between June 2001 and December 2013 were included. Results: Fifty-four patients were identified. Median age at transplant was 22 years (range 15-49 years); 26 were men and 28 were women. Forty-eight patients (89%) underwent HDCT and ASCT after achieving a radiological response to salvage chemotherapy. The rate of radiological complete response to salvage chemotherapy was 13% and reached 50% within 3 months of ASCT in assessable patients. After a median follow-up of 25 months, 31 patients (57%) were still alive with no evidence of relapse or progression. Median event-free survival (EFS) was 24 months (95% CI 8.7-39.3) and 3-year EFS was 56%. Median overall survival (OS) was not reached and 3-year OS was 82.5%. Bulky mediastinal disease at relapse, hemoglobin level, and number of salvage regimens did not significantly impact EFS in univariate and multivariate analyses. After transplantation there was a trend towards longer EFS (30 vs. 24 months; p = 0.36) in patients with a longer time from the end of first-line treatment until relapse (≥12 vs. <12 months). The 100-day transplant-related mortality was 5.5%. Conclusions: HDCT and ASCT for relapsed/refractory Hodgkin’s lymphoma is safe. Our findings are consistent with published phase III results. Longer follow-up is warranted.

Long-Term Outcome after LACE (Lomustine, Ara-C, Cyclophosphamide, Etoposide) Conditioned Autologous Stem Cell Transplantation for Relapsed or Refractory Hodgkin’s Lymphoma: A Single Centre Experience.

Blood ◽  
2005 ◽  
Vol 106 (11) ◽  
pp. 5502-5502
Author(s):  
Jolanta B. Perz ◽  
Chrissy M. Giles ◽  
Donald MacDonald ◽  
Jane F. Apperley ◽  
Edward J. Kanfer
Keyword(s):  
Stem Cell ◽  
Stem Cell Transplantation ◽  
Cell Transplantation ◽  
Autologous Stem Cell Transplantation ◽  
Hodgkin’S Lymphoma ◽  
High Dose Chemotherapy ◽  
Hodgkin's Lymphoma ◽  
Secondary Malignancy ◽  
High Dose ◽  
Long Term Outcome

Abstract Introduction: The majority of patients with Hodgkin’s lymphoma are cured with initial therapy. However, in patients with primary refractory or relapsed disease, high-dose therapy followed by autologous stem cell transplantation has been shown to be the best option. We analysed patients (pts) who underwent autologous stem cell transplantation (ASCT) following LACE (Lomustine 200 mg/m2, Ara-C 4 g/m2, Cyclophosphamide 4.8 g/m2, Etoposide 1 g/m2) conditioning for relapsed or refractory Hodgkin’s lymphoma at the Hammersmith Hospital, London, between 1991 and 2004. Patients and methods: 67 pts (46 m, 21 f) initially diagnosed with Hodgkin’s lymphoma (stage I; n=2, stage II; n=29, stage III; n=22 and stage IV; n=14) received first-line chemotherapy with ABVD or COP/ABVD (n=20), BEMOP-CA (n=29), COPP or similar (n=14) or mantle radiotherapy alone (n=4). High dose chemotherapy (HDC) with LACE and ASCT was undertaken in 45 of these pts in 1st relapse, 15 pts in 2nd or subsequent relapse and 7 pts with refractory disease. Median age at the time of HDC was 32 y (17 – 70 y). Prior to ASCT further chemotherapy achieved a complete or partial remission in 41 pts (chemosensitive), but 26 pts had no significant response (chemoresistant). Stem cells were mobilised with Etoposide (1.8 g/m2) and G-CSF in 56 pts, and bone marrow harvest was performed in the other 11 pts. Results: Two pts suffered a treatment-related mortality (TRM) within the first 100 days (3%). Two pts (3%) developed secondary malignancy (acute myeloid leukaemia). With a median follow-up of 43.3 months (range 0.5 – 145.5 months) the cumulative probabilities of overall survival (OS) and progression free survival (PFS) at both 5 and 10 years was 70% and 62% respectively. Pts who had chemosensitive disease at the time of ASCT had a better OS (p=0.008) and PFS (p=0.08) when compared with pts who had chemoresistant disease. Median PFS has not yet been reached for chemosensitive pts but was 23.4 months for chemoresistant pts. Median OS has not yet been reached for either group. Conclusions: The outcome for patients with relapsed or refractory Hodgkin’s lymphoma following high dose chemotherapy and ASCT has been sufficiently encouraging to suggest that ASCT should be considered early in chemosensitive patients. However, new therapeutic strategies are needed to improve the clinical outcome of patients with chemoresistant disease.

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