High-dose sequential chemoradiotherapy, a widely applicable regimen, confers survival benefit to patients with high-risk multiple myeloma.

Gianni, Alessandro M.; Tarella, Corrado; Bregni, Marco; Siena, Salvatore; Lombardi, Fabrizio; Gandola, Lorenza; Caracciolo, Daniele; Stern, Angelika C.; Bonadonna, Gianni; Boccadoro, Mario

doi:10.1200/jco.1994.12.3.503

Cited by 67 publications

(31 citation statements)

References 25 publications

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“…1 High-dose chemotherapy with autologous stem cell transplantation (SCT) can result in prolonged response duration and survival. [2][3][4][5][6][7][8][9] Unfortunately, few, if any, patients with MM who receive high-dose therapy are cured. 10 On the other hand, extensive clinical and experimental data support an important role for a graft-versustumor (GVT) effect in eradicating a number of different tumor cells in patients who receive allogeneic stem cell transplantation (allo-SCT).…”

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Graft-versus-myeloma effect following antithymocyte globulin-based reduced intensity conditioning allogeneic stem cell transplantation

Mohty

Boiron

Damaj

et al. 2004

Bone Marrow Transplant

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Summary:In all, 41 multiple myeloma (MM) patients received an antithymocyte globulin (ATG), fludarabine, and busulfanbased reduced intensity conditioning (RIC) for allogeneic stem cell transplantation (allo-SCT) from HLA-identical siblings. In total, 29 patients (70%) were in partial remission, one patient in complete remission, and 11 (27%) with progressive disease at the time of allo-SCT. Median time between diagnosis and allo-SCT was 24 months. The cumulative incidences of grade II-IV and grade III-IV acute graft-versus-host disease (GVHD) were 36% (95% CI, 21-51%) and 7% (95% CI, 2-20%), respectively. Overall, 10 patients developed limited chronic GVHD, whereas seven developed an extensive form (cumulative incidence, 41% (95% CI, 26-56%) at 2 years). With a median follow-up of 389 days, the overall cumulative incidence of transplant-related mortality (TRM) was 17% (95% CI, 6-28%). In all, 11 patients (27%) are in continuous complete remission, and the Kaplan-Meier estimates of overall survival (OS) and progression-free survival (PFS) at 2 years were 62% (95% CI, 47-76%) and 41% (95% CI, 23-62%), respectively. PFS and OS were significantly higher in patients with chronic GVHD as compared to patients without chronic GVHD (P ¼ 0.006 for PFS and P ¼ 0.01 for OS). Collectively, these data demonstrate that RIC allo-SCT can mediate a potentially curative graft-versusmyeloma effect with an acceptable incidence of toxicity and TRM.

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confidence: 99%

Graft-versus-myeloma effect following antithymocyte globulin-based reduced intensity conditioning allogeneic stem cell transplantation

Mohty

Boiron

Damaj

et al. 2004

Bone Marrow Transplant

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“…2 Correspondence: Dr CD Buckner, Response Oncology, Inc., 600 Broadway, Suite 112, Seattle, WA 98122, USA Received 2 January 1998; accepted 13 March 1998 Although cures following autologous stem transplantation have not been documented it is clear that this strategy improves the CR rate and prolongs survival. 1,2 Since it is unlikely that patients who do not achieve CR will have prolonged EFS [3][4][5][6][7][8][9][10][11] attempts to improve CR rates with HDC are reasonable. In order to improve CR rates in patients with multiple myeloma tandem high-dose regimens have been explored.…”

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Phase I–II evaluation of rapid sequence tandem high-dose melphalan with peripheral blood stem cell support in patients with multiple myeloma

Weaver

Zhen

Schwartzberg

et al. 1998

Bone Marrow Transplant

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Summary:This study was designed to determine the maximum tolerated dose (MTD) of high-dose melphalan (HDM), with peripheral blood stem cell support, that could be given twice within 90 days to patients with multiple myeloma. Twenty patients received tandem HDM at 160, 180 or 200 mg/m 2 and a total of 55 were treated at the estimated MTD of 200 mg/m 2 . Seventeen of 55 (31%) did not receive cycle 2; six because of low CD34 + cell yields, three because of severe (n = 1) or fatal toxicities (n = 2) and eight for other reasons. The median interval between doses for 38 patients was 70 days (range 41-225). Three of 55 patients (5%) died of treatmentrelated causes. In patients completing two cycles of HDM, at any dose level, the complete remission rate improved from 15% following cycle 1 to 55% following cycle 2. The probabilities of survival, event-free survival and relapse or progression at 18 months for the 55 patients treated at the MTD were 0.84, 0.76 and 0.20, respectively, with a median follow-up of 19 months (range 9-36) from mobilization chemotherapy. It was concluded that two cycles of HDM, 200 mg/m 2 , could be administered to approximately 70% of patients under the age of 66 with multiple myeloma in a median interval of 70 days, with improvement in CR rates. Keywords: melphalan; myeloma The Intergroupe Français du Myelome (IFM) demonstrated superiority in response, overall survival (OS) and eventfree survival (EFS) following high-dose chemotherapy (HDC) and total body irradiation (TBI) with bone marrow (BM) support for patients with newly diagnosed multiple myeloma under the age of 65, compared to conventionaldose chemotherapy. 1 Complete remissions (CR) were achieved in 5% of conventionally treated patients and 22% of patients receiving autologous BM transplants. 1 A recent 6 year follow-up shows a 21% survival for the conventional group compared to 43% for the transplant group (P = 0.03). Although cures following autologous stem transplantation have not been documented it is clear that this strategy improves the CR rate and prolongs survival. 1,2 Since it is unlikely that patients who do not achieve CR will have prolonged EFS 3-11 attempts to improve CR rates with HDC are reasonable. In order to improve CR rates in patients with multiple myeloma tandem high-dose regimens have been explored. 12 When considering tandem or sequential high-dose treatments it is generally thought to be important to deliver such therapy within a short period of time. 13 Previous studies have demonstrated the feasibility of administering two cycles of HDM at 200 mg/m 2 but the minimum time interval between doses supported by PBSC has not been established. 12 The purpose of the current study was to determine the maximum tolerated doses (MTD) of HDM supported by peripheral blood stem cells (PBSC) that could be given within 90 days and to evaluate the effect of this strategy on response rates, especially in patients who had only received initial induction chemotherapy. March 1994 and 15 September 1995, 78 patients with multiple my...

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“…High-dose chemotherapy (HDC) with autologous haematopoietic progenitor support is a promising approach for increasing the dose intensity of first-line treatment in patients with high-risk cancer who respond to conventional therapy (McMillan et al, 1991;Peters et al, 1993a;Wheeler et al, 1993;Ayash et al, 1994;Gianni et al, 1994;Benedetti Panici et al, 1995). Unfortunately, HDC is limited by significant morbidity and mortality related to haematological and non-haematological toxicities.…”

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High-dose carboplatin, etoposide and melphalan (CEM) with peripheral blood progenitor cell support as late intensification for high-risk cancer: non-haematological, haematological toxicities and role of growth factor administration

Panici¹,

Pierelli²,

Scambia³

et al. 1997

Br J Cancer

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Summary The present report describes the non-haematological toxicity and the influence of growth factor administration on haematological toxicity and haematopoietic recovery observed after high-dose carboplatin (1200 mg m-2), etoposide (900 mg m-2) and melphalan (100 mg m-2) (CEM) followed by peripheral blood progenitor cell transplantation (PBPCT) in 40 patients with high-risk cancer during their first-line treatment. PBPCs were collected during the previous outpatient induction chemotherapy programme by leukaphereses. CEM administration with PBPCT was associated with low non-haematological toxicity and the only significant toxicity consisted of a reversible grade III/IV increase in liver enzymes in 32% of the patients. Haematopoietic recovery was very fast in all patients and the administration of granulocyte colony-stimulating factor (G-CSF) plus erythropoietin (EPO) or granulocyte-macrophage colony-stimulating factor (GM-CSF) plus EPO after PBPCT significantly reduced haematological toxicity, abrogated antibiotic administration during neutropenia and significantly reduced hospital stay and patient's hospital charge compared with patients treated with PBPCT only. None of the patients died early of CEM plus PBPCTrelated complications. Low non-haematological toxicity and accelerated haematopoietic recovery renders CEM with PBPC/growth factor support an acceptable therapeutic approach in an adjuvant or neoadjuvant setting.

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High-dose sequential chemoradiotherapy, a widely applicable regimen, confers survival benefit to patients with high-risk multiple myeloma.

Abstract: HDS emerges as a highly effective, well-tolerated, and widely accessible regimen capable of imparting a survival benefit to patients with high-LI multiple myeloma. Larger studies using this or similar programs in standard-risk myeloma are clearly warranted.

Cited by 67 publications

References 25 publications

Graft-versus-myeloma effect following antithymocyte globulin-based reduced intensity conditioning allogeneic stem cell transplantation

Graft-versus-myeloma effect following antithymocyte globulin-based reduced intensity conditioning allogeneic stem cell transplantation

Phase I–II evaluation of rapid sequence tandem high-dose melphalan with peripheral blood stem cell support in patients with multiple myeloma

High-dose carboplatin, etoposide and melphalan (CEM) with peripheral blood progenitor cell support as late intensification for high-risk cancer: non-haematological, haematological toxicities and role of growth factor administration

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