Intensified and high-dose chemotherapy with granulocyte colony-stimulating factor and autologous stem-cell transplantation support as first-line therapy in high-risk diffuse large-cell lymphoma.

Vitolo, Umberto; Cortellazzo, S.; Liberati, A. M.; Freilone, Roberto; Falda, Michele; Bertini, M; Botto, Barbara; Cinieri, Saverio; Levis, Alessandro; Locatelli, Franco; Lovisone, E; Marmont, Filippo; Pizzuti, Michele; Rossi, Andrea; Viero, Piera; Barbui, Tiziano; Grignani, F; Resegotti, L

doi:10.1200/jco.1997.15.2.491

Cited by 55 publications

(36 citation statements)

References 27 publications

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“…Thirty patients were treated with MACOP-B for 8 weeks, followed by intensification with a 3-day course of mitoxantrone 8 mg/m 2 plus high-dose Ara-C (2 g/m 2 every 12 h) 12 and granulocyte colony-stimulating factor to harvest PBPCs; conditioning regimen consisted of carmustine, etoposide, Ara-C and melphalan regimen followed by autografting. The policy of the centres involved in the two study protocols was to perform the autografting procedure with a minimum amount of 5 Â 10 6 CD34-positive cells/kg of recipient body weight.…”

Section: Treatment Planmentioning

confidence: 99%

Long-term follow-up of patients with peripheral T-cell lymphomas treated up-front with high-dose chemotherapy followed by autologous stem cell transplantation

et al. 2006

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We report the results of two prospective phase II studies investigating the role of high-dose sequential chemotherapy, followed by autologous stem cell transplantation (ASCT) in 62 patients with advanced stage peripheral T-cell lymphomas (PTCLs) at diagnosis. Conditioning regimen consisted of mitoxantrone (60 mg/m 2 ) and melphalan (180 mg/m 2 ) or carmustine, etoposide, Ara-C and melphalan followed by peripheral blood stem cell autografting. In an intent-to-treat analysis, 46 out of 62 patients (74%) completed the whole programme, whereas 16 patients did not undergo ASCT, mainly because of disease progression. At a median follow-up of 76 months, the estimated 12-year overall (OS), disease-free and event-free survival (EFS) were 34, 55 and 30%, respectively. OS and EFS were significantly better in patients with anaplastic lymphomakinase (ALK)-positive anaplastic large-cell lymphoma (ALCL), as compared with the remaining PTCL. Multivariate analysis showed that patients attaining complete remission (CR) before ASCT had a statistically significant benefit in terms of OS and EFS (Po0.0001). Overall treatment-related mortality rate was 4.8%. In conclusion, our findings indicate (1) up-front high-dose therapy and ASCT are feasible, but could induce a high rate of long-term CR only in patients with ALK-positive ALCL and (2) the achievement of CR before autografting is a strong predictor of better survival.

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Section: Treatment Planmentioning

confidence: 99%

Long-term follow-up of patients with peripheral T-cell lymphomas treated up-front with high-dose chemotherapy followed by autologous stem cell transplantation

et al. 2006

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“…Pilot studies performed in specialized institutions are also warranted, and two merit more detailed discussion. The prospective cooperative trial reported by Vitolo et al 20 involved 50 patients with high-risk LCL. They were assigned to receive a programme which consisted of the following three phases: induction with 8 weeks of MACOP-B, intensification with high-dose cytarabine plus mitoxantrone and dexamethasone, and consolidation with BEAM therapy supported by ASCT.…”

Section: Discussionmentioning

confidence: 99%

“…With a median followup of 32 months, OS and DFS were at 56% and 69%, respectively. 20 In another pilot study, the role of HDT with ABMT/ASCT during first CR or PR was assessed in 52 patients with poor-risk intermediate and high-grade lymphoma. The authors reported a 3-year DFS of 89% in the subset of patients with LCL, with 92% and 87% in the HI risk and H risk groups, respectively.…”

Section: Discussionmentioning

confidence: 99%

Role of high-dose therapy and initial response in survival of poor-risk patients with aggressive non-Hodgkin's lymphoma: a retrospective series on 126 patients from a single center

Bouabdallah

Coso

Costello

et al. 2000

Bone Marrow Transplant

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Summary:It is now established that a subgroup of non-Hodgkin's lymphoma (NHL) patients probably benefit from highdose therapy (HDT). We therefore retrospectively analyzed survival of 126 consecutive patients with large cell lymphoma (LCL) and high-intermediate (HI) or highrisk (H) age-adjusted international prognostic index (Aa-IPI). They received either standard chemotherapy (CT) (66 patients), or HDT (60 patients). Distribution of the Aa-IPI scores showed no statistical significant difference between the two treatment groups. Complete response (CR) rate was 51% for the whole series, with 41% and 62% for the standard CT group and HDT group, respectively. With a median follow-up of 63 months (range, 16 to 159), the 5-year overall survival (OS) and event-free survival (EFS) for all patients was 52% and 43%, respectively. There was a statistical significant difference in terms of survival towards the HDT group: OS at 76% vs 31%, EFS at 64% vs 24%. Patients who achieved CR with front-line therapy had a 5-year OS at 70%, while it was 34% for patients who were not in CR. These results are comparable to those reported in the literature, and strongly suggest that both initial CR achievement and HDT as front-line treatment are predictive factors for prolonged survival of patients with poor-risk LCL. Bone Marrow Transplantation (2000) 25, 35-40. Keywords: aggressive lymphoma; standard chemotherapy; high-dose therapy; complete response; survival Among non-Hodgkin's lymphomas (NHL), large cell lymphomas (LCL) have been recently well characterized in the Revised European-American Lymphoma (REAL) classification. 1 The CHOP regimen (doxorubicine, cyclophosphamide, vincristine, prednisone) has been extensively used in the treatment of LCL patients, and may cure approximately 30% of patients. 2 Many combination chemotherapy regimens modeled after CHOP have been tested in order

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“…The Table 1 Intensified sequential and high-dose chemotherapy with autologous transplantation in patients with lymphoma CR rate was 72.5% and actuarial 3-year EFS and overall survival was 40% and 48%, respectively. Vitolo et al 21 treated 50 high-risk DLCL patients with 8 weeks of induction MACOPB, followed by intensification with mitoxantrone (24 mg/m 2 ), cytarabine (12 g/m 2 ) and dexamethosone (24 mg/m 2 )(MAD). Thirty-nine patients (78%), achieving at least a PR, were consolidated with BEAM and PBPC support.…”

Section: Tandem Intensive Sequential Chemotherapy and Autologous Tranmentioning

confidence: 99%

“…This dose-intense strategy has been applied as both first-line and salvage therapy to poor risk patients Ͻ60 years (Table 1). [18][19][20][21][22] Two pilot studies of intensive sequential chemotherapy as first-line treatment in patients with aggressive NHL were conducted by Bouaddallah and colleagues. 23 For study ISC 92, patients received three cycles of high-dose CHOP (cyclophosphamide 3 g/m 2 , doxorubicin 75 mg/m 2 , vincristine 2 mg, and prednisone 60 mg/m 2 for 5 days) followed by three intensified stem cell supported cycles of high-dose CHOP with etoposide (300 mg/m 2 ) and cisplatin (100 mg/m 2 ).…”

Section: Tandem Intensive Sequential Chemotherapy and Autologous Tranmentioning

confidence: 99%

Tandem transplantation in lymphoma

Papadopoulos

Noguera-Irizarry

Hesdorffer

2001

Bone Marrow Transplant

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Summary:The majority of poor-risk lymphoma patients are not cured with conventional chemotherapy. There is evidence for the superiority of single high-dose chemotherapy in such patients, but many still die from recurrent disease. Strategies to improve survival in these poor-risk patients include dose-intensification with high-dose chemotherapy and PBPC support, tandem autologous HDC with PBPC support, and autologous followed by non-myeloablative allogeneic transplantation. These more aggressive strategies are feasible and tolerable. Whether tandem transplantation will prove more effective than current single high-dose therapy in appropriately selected patients remains to be determined. Bone Marrow Transplantation (2001) 28, 529-535. Keywords: tandem transplantation; lymphoma; autologous; allogeneicThe majority of patients with lymphoma achieve remission with standard therapy. A small percentage of patients are refractory to initial therapy, and approximately one-third of patients with stage III-IV disease will relapse after achieving a complete response. Treatment of minimally responsive or refractory lymphoma patients remains a challenge. Single transplantation and the poor prognosis patientProspective randomized trials show single HDC with autologous transplantation to be superior to standard-dose chemotherapy for relapsed and resistant Hodgkin's disease, 1 for consolidative therapy of poor-risk B cell NHL in first remission 2 and for relapsed chemo-sensitive intermediate or high-grade NHL. 3 An update of the PARMA study reports an 8-year EFS of 36% and OS of 47% for these latter patients. 4 Fewer than 5% of patients with poor-risk NHL or HD who have induction failure and receive conventional salvage chemotherapy are alive at 5 years. NHL patients with induction failure who undergo HDC and autotransplantation have an overall survival at 5 years of 37%. 5 Data from the ABMTR show HD patients with induction Correspondence: DR CS Hesdorffer, Division of Medical Oncology, MHB 6N 435, 177 Ft. Washington Avenue, New York, NY 10032, USA failure who subsequently undergo HDC have progressionfree and overall survivals at 3 years of 38% and 50%, respectively. 6 Data by Sweetenham et al 7 from the EBMT are similar, reporting an actuarial 5-year OS rate of 36% and PFS rate of 32%.Allogeneic transplantation alone does not appear to offer a survival advantage over autologous transplant for lymphoma. 8,9 Studies suggest a graft-versus-lymphoma effect, but this has not translated into increased survival due to the high treatment-related mortality associated with allogeneic transplantation. Further prospective trials, randomized on the basis of HLA-identical donor availability, may provide more reliable data on this issue. 10 While salvage rates of 45-60% are achieved with HDC in patients with relapsed NHL and HD with good prognostic factors, adverse prognostic factors, such as relapse within 1 year of initial treatment, stage III/IV relapse or chemoresistance, portend a poorer outcome, with likely cure in less than 40%. The IP...

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Intensified and high-dose chemotherapy with granulocyte colony-stimulating factor and autologous stem-cell transplantation support as first-line therapy in high-risk diffuse large-cell lymphoma.

Abstract: This sequential scheme with intensified and high-dose chemotherapy with ASCT is feasible with moderate toxicity and may improve the outcome in high-risk DLCL.

Cited by 55 publications

References 27 publications

Long-term follow-up of patients with peripheral T-cell lymphomas treated up-front with high-dose chemotherapy followed by autologous stem cell transplantation

Long-term follow-up of patients with peripheral T-cell lymphomas treated up-front with high-dose chemotherapy followed by autologous stem cell transplantation

Role of high-dose therapy and initial response in survival of poor-risk patients with aggressive non-Hodgkin's lymphoma: a retrospective series on 126 patients from a single center

Tandem transplantation in lymphoma

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