Dose Intensity of Chemotherapy in Patients With Relapsed Hodgkin's Lymphoma

2010 ◽  
Vol 28 (34) ◽  
pp. 5074-5080 ◽  
Author(s):  
Andreas Josting ◽  
Horst Müller ◽  
Peter Borchmann ◽  
Joke W. Baars ◽  
Bernd Metzner ◽  
...  
Keyword(s):  
Hodgkin’S Lymphoma ◽  
Stage Iv ◽  
Dose Intensity ◽  
High Dose Chemotherapy ◽  
Observation Time ◽  
Hodgkin's Lymphoma ◽  
High Dose ◽  
Significant Difference ◽  
Multiple Relapse ◽  
The Impact

Purpose High-dose chemotherapy (HDCT) followed by autologous stem-cell transplantation (PBSCT) has become the standard treatment for patients with relapsed Hodgkin's lymphoma (HL). The intensity of treatment needed is unclear. This European intergroup study evaluated the impact of sequential high-dose chemotherapy (SHDCT) before myeloablative therapy. Patients and Methods Patients with histologically confirmed, relapsed HL were treated with two cycles of dexamethasone, cytarabine, and cisplatin, and those without disease progression were randomly assigned. In the standard arm (A), patients received myeloablative therapy with carmustine, BEAM (carmustine, etoposide, cytarabine, and melphalan) followed by PBSCT. Patients in the experimental arm (B) also received sequential cyclophosphamide, methotrexate, and etoposide in high-doses before BEAM. Freedom from treatment failure (FFTF) was the primary end point. Remission rates, overall survival (OS), and toxicity of treatment were secondary end points. Results From a total of 284 patients included, 241 responding patients were randomly assigned after two cycles of dexamethasone, cytarabine, and cisplatinum. Patients treated in arm B had longer treatment duration and experienced more toxicity and protocol violations (P < .05). Mortality was similar in both arms (20% and 18%). With a median observation time of 42 months, there was no significant difference in terms of FFTF (P = .56) and OS (P = .82) between arms. FFTF at 3 years was 62% (95% CI, 56% to 68%) and OS was 80% (95% CI, 75% to 85%). Patients with stage IV, early relapse, multiple relapse, anemia, or B symptoms had a higher risk of recurrence (P < .001). Conclusion Compared with conventional high-dose chemotherapy, additional SHDCT is associated with more adverse effects and does not improve the prognosis of patients with relapsed HL.

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

Intensive sequential chemotherapy with repeated blood stem-cell support for untreated poor-prognosis non-Hodgkin's lymphoma.

1997 ◽  
Vol 15 (5) ◽  
pp. 1722-1729 ◽  
Author(s):  
A M Stoppa ◽  
R Bouabdallah ◽  
C Chabannon ◽  
G Novakovitch ◽  
N Vey ◽  
...  
Keyword(s):  
Stem Cell ◽  
Median Duration ◽  
Hodgkin’S Lymphoma ◽  
Dose Intensity ◽  
Blood Stem Cell ◽  
Hodgkin's Lymphoma ◽  
High Dose ◽  
Sequential Chemotherapy ◽  
Free Survival ◽  
Non Hodgkin's Lymphoma

PURPOSE To demonstrate the feasibility and efficacy of six ambulatory high-dose sequential chemotherapy courses that include three intensified cycles supported by stem-cell infusion in high-risk and high-intermediate-risk untreated non-Hodgkin's lymphoma (NHL) patients. PATIENTS AND METHODS A pilot nonrandomized study included 20 untreated patients aged less than 60 years with aggressive histologically identified NHL and two or three adverse-prognosis criteria (International Index). Patients received an ambulatory regimen with high-dose chemotherapy supported by granulocyte colony-stimulating factor (G-CSF) and repeated peripheral-blood stem-cell (PBSC) infusion. The median age was 39 years (range, 20 to 59), with 13 men and seven women. Chemotherapy consisted of one cycle every 21 days for a total of six cycles. The first three cycles (A1, A2, and A3) consisted of cyclophosphamide (Cy) 3,000 mg/m2, doxorubicin (Doxo) 75 mg/m2, and vincristine 2 mg (plus corticosteroids). The last three cycles (B4, B5, and B6) consisted of the same drug combination plus etoposide 300 mg/m2 and cisplatin 100 mg/m2. For an expected duration of 18 weeks, the projected dose-intensity was 25 mg/m2/wk for Doxo and 1,000 mg/m2/wk for Cy. G-CSF 300 micrograms was administered from day 6 following each cycle until neutrophil reconstitution. Two aphereses were performed at approximately day 13 after each A cycle, and PBSCs were injected at day 4 of each B cycle. Radiotherapy on tumor masses > or = 5 cm was scheduled after completion of the last cycle. RESULTS The median duration of grade 4 neutropenia was 1 day (range, 0 to 7) for each A cycle and 4 days (range, 1 to 10) for each B cycle (P = .02). The median duration of grade 4 thrombopenia was 0 days (range, 0 to 8) for each A cycle and 6 days (range, 1 to 21) for each B cycle (P < .001). Hospitalization for febrile neutropenia was required for 18% and 44% of patients during cycles A and B, respectively (P < .01). Only three patients did not complete the protocol: one due to emergency surgery after cycle B4, one who died after cycle B5 from interstitial pneumonia, and one with delayed hematologic reconstitution after cycle B4. Chemotherapy delivery was optimal (median actual relative dose-intensity, 97%; range, 66 to 100). The median total dose administered over 18 weeks was 18,000 mg Cy (range, 12,000 to 18,000), 450 mg Doxo (range, 300 to 450), 900 mg etoposide (range, 300 to 900), and 300 mg cisplatin (range, 100 to 300). Evaluation of response after six courses showed 13 complete remissions ([CRs] 65%), four partial remissions (PRs), two nonresponses (NRs), and one toxic death. With a median follow-up period of 25 months (range, 16 to 43), 15 patients are alive, with 12 in continuous first CR; five patients relapsed (four of four PRs and one of 13 CRs). Two-year survival and failure-free survival (FFS) rates are 73% and 56%, respectively. The disease-free survival (DFS) rate for the CRs is 86%. CONCLUSION PBSC support contributes to the feasibility of first-line, very-high-dose, ambulatory chemotherapy delivery in poor-risk NHL and is associated with a high rate of remission and FFS.

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.

The Utility of Consolidative Upfront High Dose Chemoradiotherapy and ASCT in Patients with Mantle Cell Lymphoma (MCL).

Blood ◽  
2005 ◽  
Vol 106 (11) ◽  
pp. 2072-2072
Author(s):  
Daniel Persky ◽  
Carol S. Portlock ◽  
Simone Lessac-Chenen ◽  
Alexia Iasonos ◽  
Andrew D. Zelenetz ◽  
...  
Keyword(s):  
Bone Marrow Involvement ◽  
Conditioning Regimen ◽  
Stage Iv ◽  
Progression Free Survival ◽  
High Dose Chemotherapy ◽  
High Dose ◽  
Significant Difference ◽  
Dose Dense

Abstract Introduction: Two approaches to improve progression-free survival (PFS) in MCL are intensifying induction, as with hyperCVAD/M-A regimen, or intensifying consolidation with high dose chemoradiotherapy (HDT) and ASCT as in the prospective European MCL Network Trial. At MSKCC the strategy is to incorporate both approaches by administering an anthracycline-containing regimen in a dose dense fashion (CHOP- or R-CHOP-14) followed by consolidation with ICE (ifosfamide, carboplatin, etoposide) and HDT/ASCT. Patients: Forty six patients with newly diagnosed MCL underwent HDT/ASCT between 11/96 and 2/05. The median age was 55 years; 74% were male; 72% had bone marrow involvement, 39% had GI involvement, 7% were in leukemic phase, and 91% presented with stage IV disease. Splenomegaly was seen in 35%, B symptoms in 9%, KPS>70 in 93%, elevated LDH in 23%, and blastoid histology in 9%. Results: Induction was 4 to 6 cycles of CHOP-14 (43%), R-CHOP-14 (37%), or other doxorubicin-containing regimen (20%). Consolidation was performed with 2–3 cycles of ICE in 53% or R-ICE in 39%. Upfront treatment was well tolerated and permitted adequate stem cell collection and prompt transition to HDT/ASCT. Conditioning regimens were TBI/CY/VP-16 (59%) and BEAM (41%). Involved field radiation therapy was administered to 65%. Post-ASCT rituximab maintenance was given to 39%, with 57% of patients receiving rituximab as part of their treatment. Anthracycline-based induction led to CRu of 44% and ORR of 98%. Seventy two percent of patients were transplanted in CR, while the remaining 28% were in PR. At a median follow-up of 2.5 years (range 0.4–8.0 years) 17% of the patients have died and 24% have had progressive disease. The median OS and PFS have not been reached (lower 95% CI, 5.7 years and 4.4 years, respectively). The 5-year PFS and OS are 58% and 83%, respectively. The use of rituximab at any point during treatment prolonged PFS - only 1 of 26 patients receiving rituximab relapsed, as compared to 10 of 20 patients who were rituximab naive (p=0.03); thus far there is no significant difference in OS. There was no day 100 treatment related mortality. One patient developed bronchiolitis obliterans after ASCT and died of pulmonary fibrosis 6.5 years later; 3 patients have died of secondary cancers - one case each of MDS (1.6 years after ASCT), melanoma and lung cancer. Conclusion: These data provide evidence that dose-dense induction with CHOP-14 or R-CHOP-14 and consolidation with ICE/HDT/ASCT appears to be safe and effective, with minimal acute toxicity. Although the median follow-up is short, the use of rituximab appears to improve PFS. This contrasts with the findings of German LGLSG and may be a consequence of in vivo rituximab purging. Future therapy could incorporate all the successful elements of prior treatment programs, including R-CHOP-14, R-ICE, and radioimmunotherapy with high dose chemotherapy conditioning regimen, followed by ASCT and rituximab-based maintenance. PFS stratified by Rituximab PFS stratified by Rituximab

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.

Busulfan, Melphalan and Etoposide Followed by Autologous Stem Cell Transplantation on Patients with Non-Hodgkin's Lymphoma: Multicenter Study From Consortium for Improving Survival of Lymphoma (CISL) in Korea

Blood ◽  
2011 ◽  
Vol 118 (21) ◽  
pp. 2021-2021
Author(s):  
Kyoung Ha Kim ◽  
Won Seog Kim ◽  
Sung-Kyu Park ◽  
Mark Hong Lee ◽  
Sang Kyun Sohn ◽  
...  
Keyword(s):  
Stem Cell ◽  
High Risk ◽  
Stem Cell Transplantation ◽  
Cell Transplantation ◽  
Autologous Stem Cell Transplantation ◽  
Hodgkin’S Lymphoma ◽  
High Dose Chemotherapy ◽  
Hodgkin's Lymphoma ◽  
High Dose ◽  
Non Hodgkin's Lymphoma

Abstract Abstract 2021 Background: High dose chemotherapy followed by autologous stem cell transplantation (ASCT) has become the standard approach for relapsed or high risk non-Hodgkin's lymphoma (NHL). Several different high dose therapy (HDT) conditioning regimens have been used for non-Hodgkin's lymphoma (NHL), such as BEAM (carmustine, etoposide, cytosine arabinoside, melphalan), BEAC (carmustine, etoposide, cytosine arabinoside, cyclophosphamide), and CBV (cyclophosphamide, carmustine, etoposide). Carmustine is an active drug in the HDT of NHL but the supply of carmustine is limited in some countries including Korea. Intravenous busulfan containing regimens as conditioining regimen have been used for both allogeneic and autologous stem cell transplantation in patients with hematologic and non –hematologic malignancies. The purpose of this prospective multicenter phase II study was evaluate the efficacy and safety of iv busulfan/melphalan/etoposide regimen as a conditioining regimen for high dose chemotherapy in the patients with relapsed or high risk NHL. Methods: Patients with relapsed or primary refractory NHL or chemosensitive high risk NHL underwent high dose chemotherapy followed by ASCT at 13 centers in Korea. The conditioning regimen consisted of iv busulfan 3.2mg/kg/day i.v. on days −8, −7 and −6, etoposide 400mg/m2/day i.v. on days −5 and −4 and melphalan 50mg/m2/day i.v. on days −3 and −2. Results: Fifty one patients were enrolled onto the study. Main subgroups were DLBCL (n=25, 49%) and T cell lymphoma (n=19, 37%). At the time of ASCT, the disease status of patients was as follows: 13 patients were high risk in remission, 16 were primarily refractory to inducton therapy, 15 patients were in chemosensitive relapse. All patients had successful stem cell engraftment with a median time to neutrophil recovery of more than 500/mm3 of 10 days (range, 2 to 30 days). Platelet recovery of more than 20,000/mm3 was seen after a median of 10 days (range, 2 to 51 days) with delayed recovery in one patient. Treatment related toxicities included nausea/vomiting in 28 patients (55%), diarrhea in 28 patients (55%) and mucositis in 33 patients (65%), which were grade I or II in the majority of cases. Grade I/II hepatic toxicities occurred in 24% (n=12) and grade III in 6% (n=3). There were no VOD and treatment related death. The median duration of hospitalization for ASCT was 30 days (range, 12 to 80 days). Forty one patients (80%) achieved a complete response 1 month after ASCT, while three patients showed progressive disease. At a median follow up of 14.7 months, 21(41%) patients exhibited a relapse or progression, while 11 patients had died of disease and one patient had died of heart failure. The estimated 2-year overall and progression free survival for all patients was 64% and 40%, respectively. Conclusion: This preliminary analysis suggests that conditioning regimen of i.v. busulfan/melphalan/etoposide would be well tolerated and effective in patients with relapsed or high risk NHL. Accordingly, this regimen may be regarded as an important treatment option to substitute for BEAM regimen. Disclosures: Lee: Novartis: Research Funding.

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