Haematological support of high-dose sequential chemotherapy: Clinical evidence for reduction of toxicity and high response rates in poor risk lymphomas

Tarella, Corrado; Gavarotti, Paolo; Caracciolo, Daniele; Corradini, Paolo; Cherasco, C; Castellino, Claudia; Gallo, E.; Pileri, Alessandro

doi:10.1093/annonc/6.suppl_4.s3

Cited by 21 publications

(27 citation statements)

References 21 publications

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“…This adverse event further supports a preferential use of PBPC in these patients in order to minimize infectious and hemorrhagic risks related to prolonged pancytopenia. 35,36 There were few infectious complications, with incidence and severity analogous to those previously reported in HDS programs. 25,35 Despite the intensive treatment, PBPC could be harvested in sufficient amounts to perform autograft in most patients, as already reported in a previous study.…”

Section: Figuresupporting

confidence: 73%

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Long-term follow-up of advanced-stage low-grade lymphoma patients treated upfront with high-dose sequential chemotherapy and autograft

et al. 2000

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Long-term outcome, after first line intensified high-dose sequential (i-HDS) chemotherapy, was evaluated in 46 patients, aged р65 years, with advanced low-grade lymphoma. Seventeen patients had small lymphocytic lymphoma (SLL), 29 had follicular lymphoma (FL), 10 of them with histologic transformation. I-HDS included: (1) tumor debulkying, by 2 APO+2 DHAP courses; (2) sequential administration of high-dose (hd) etoposide, methotrexate, and cyclophosphamide, followed by peripheral blood progenitor cell (PBPC) harvest; (3) hd-mitoxantrone + melphalan with PBPC autograft. Ten FL patients had their PBPC immunologically purged ex vivo. There were two treatment-related deaths; five FL patients had short-lasting response followed by disease progression, five SLL reached a stable PR; overall, 34 patients (74%) reached CR. At a median follow-up of 4.3 years, the estimated 9-year OS and EFS were 84% and 45%, respectively. No significant differences were observed in the OS among patients at low, intermediate or high IPI score, with an estimated OS projection of 95%, 78%, and 75%, respectively. FL had longer survival without evidence of residual disease (9-year EFS: 59%) as compared to SLL patients (8.8-year EFS: 17%); however, both groups had prolonged survival and no need of salvage treatment, as shown by the time to disease progression curve, projected to 66% and 62% for SLL and FL, respectively. The results indicate that hdapproach in low-grade lymphoma: (1) is associated with longer progression-free survival as compared to conventional therapies; (2) may imply higher tumor mass reduction in FL as compared to SLL patients; (3) offers long life expectancy, with potential survival benefits at least for patients at intermediate/high IPI score. Leukemia (2000) 14, 740-747.

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Section: Figuresupporting

confidence: 73%

“…35,36 There were few infectious complications, with incidence and severity analogous to those previously reported in HDS programs. 25,35 Despite the intensive treatment, PBPC could be harvested in sufficient amounts to perform autograft in most patients, as already reported in a previous study. 30 This is an important aspect of our program.…”

Section: Figuresupporting

confidence: 73%

Long-term follow-up of advanced-stage low-grade lymphoma patients treated upfront with high-dose sequential chemotherapy and autograft

et al. 2000

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“…14 In the current study, rates of transplant-related mortality observed within the first 100 days and long-term (4% and 4%, respectively) appear in accordance with the incidence reported by others. 7,[17][18][19] It is worth noting that when comparing the 150 early with the 150 later PBPC transplants, the 100-day treatment-related death rate decreased from 6% to 2%, probably reflecting an improvement in supportive care and better assessment of the harvest quality, but also selection of patients with a shorter disease history before high-dose therapy.…”

Section: Discussionmentioning

confidence: 99%

“…15 Furthermore, PBPC transplants have been shown to result in less morbidity than bone marrow transplants, 11,16 even though the toxic death rate in experienced centers is around 4 to 6%. [17][18][19] We describe 300 consecutive PBPC transplants performed in a single institution in patients with lymphoproliferative diseases. The goal of the study was to analyze the different factors affecting toxicity of this procedure and to assess precisely late morbidity and mortality related to intensive chemotherapy.…”

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confidence: 99%

Toxicities after peripheral blood progenitor cell transplantation for lymphoid malignancies: analysis of 300 cases in a single institution

Ketterer

Sonet

Dumontet

et al. 1999

Bone Marrow Transplant

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Summary:Two hundred and seventy-seven consecutive patients with non-Hodgkin's lymphoma (n = 207), Hodgkin's disease (n = 27) and multiple myeloma (n = 43) were intensified from October 1989 until April 1997 and received unmanipulated PBPC transplants. Twentythree patients received a double intensification, out of a total of 300 PBPC transplantations analyzed. Conditioning regimens consisted of total body irradiation (TBI)-containing regimens (n = 141), BEAM (n = 104), highdose melphalan (n = 26), ICE (n = 23) or other regimens (n = 6). Eighty-four percent of the patients (119/142) evaluable for long-term hematological reconstitution beyond 180 days achieved normal trilineage blood counts. Abnormal hematological parameters were associated with low numbers of CD34 + cells re-infused and with prior exposure to fludarabine. The 100-day and long-term treatment-related mortality rates were 4% and 4%, respectively. Late complications and treatment-related toxicities were influenced by disease history, use of TBI and exposure to fludarabine. Patients older than 60 years did not have greater toxicities or more frequent treatment-related deaths. This analysis suggests that while leading to a limited morbidity and a low mortality rate, intensive chemotherapy with PBPC transplantation still remains a procedure leading to significant short-and long-term toxicities. Better recognition of the risk factors associated with these complications might allow a further decrease in their incidence.

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“…All these regimens were originally designed as rituximab-free schedules specifically tailored for the various lymphoma subtypes and proved feasible with acceptable toxicity when delivered without monoclonal antibody supplementation. [46][47][48] Only minor modifications have been introduced to the R-HDS regimens compared to rituximab-free schedules. These modifications are detailed below.…”

Section: Treatment Protocolmentioning

confidence: 99%

Concurrent administration of high-dose chemotherapy and rituximab is a feasible and effective chemo/immunotherapy for patients with high-risk non-Hodgkin's lymphoma

et al. 2001

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The aim of this study was to investigate feasibility, tolerability and efficacy of rituximab-supplemented high-dose sequential chemotherapy (R-HDS) with peripheral blood progenitor cell autografting as frontline or salvage treatment in patients with advanced non-Hodgkin's lymphoma (NHL). Thirty-two patients have been treated: 14 at disease onset and 18 with relapsed or progressive disease. R-HDS regimens included six courses of rituximab. Rituximab was delivered either concurrently with high-dose chemotherapy to exploit the in vivo purging properties of the drug as well as at the end of the treatment plan to target minimal residual disease. All patients treated at disease onset completed their treatment with no life-threatening toxicity, while two toxic deaths due to severe bilateral pneumonia were observed among patients treated due to relapsed or refractory disease. Thirteen of 14 patients treated up-front achieved CR. Among pre-treated patients 10 of 18 achieved CR with better results in patients with relapsed (seven of eight) compared to progressive disease (three of 10). PCR analysis was carried out in indolent lymphoma patients: nine of nine follicular lymphomas and three of six CD5-positive NHL collected PCR-negative peripheral blood progenitor cell harvests. The results of this pilot study show that R-HDS is feasible and effective with acceptable toxicity when used at disease onset. In pretreated patients this treatment also showed promising results, although the risk of severe infections needs to be considered. Leukemia (2001Leukemia ( ) 15, 1941Leukemia ( -1949

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Haematological support of high-dose sequential chemotherapy: Clinical evidence for reduction of toxicity and high response rates in poor risk lymphomas

Cited by 21 publications

References 21 publications

Long-term follow-up of advanced-stage low-grade lymphoma patients treated upfront with high-dose sequential chemotherapy and autograft

Long-term follow-up of advanced-stage low-grade lymphoma patients treated upfront with high-dose sequential chemotherapy and autograft

Toxicities after peripheral blood progenitor cell transplantation for lymphoid malignancies: analysis of 300 cases in a single institution

Concurrent administration of high-dose chemotherapy and rituximab is a feasible and effective chemo/immunotherapy for patients with high-risk non-Hodgkin's lymphoma

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