High–dose melphalan with autologous bone marrow transplant treatment of poor prognosis tumors

Corringham, Robert; Gilmore, M. J. M. L.; Prentice, HG; Boesen, Evelyn

doi:10.1002/1097-0142(19831115)52:10<1783::aid-cncr2820521004>3.0.co;2-h

Cited by 56 publications

(16 citation statements)

References 16 publications

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“…All reported no significant difference in the degree or duration of myelosuppression as the dose of melphalan increased and it would therefore seem reasonable to compare ours with other series. The median durations of neutropenia (< 0.5 x I091') and thrombocytopenia ( < 20 x 109 ') were 14-28 days and 20-26 days respectively in these studies (Hartmann et al, 1986;Lazarus et al, 1983;Corringham et al, 1983). In our study using GM-CSF, the median duration of neutropenia of 14 days is a similar duration to that seen with ABMR, and the median duration of thrombocytopenia of 10 days may be shorter.…”

Section: Patientssupporting

confidence: 53%

“…Single agent melphalan was chosen because of its predictable pharmacokinetics with rapid serum elimination (Ardiet et al, 1986) and because of the demonstration that at doses > 100 mg m2, responses could be induced in a wide range of advanced haematological and solid tumours (McElwain et al, 1979;Lazarus et al, 1983;Corringham et al, 1983;Cornbleet et al, 1983;Hartmann et al, 1986). Haematological toxicity of melphalan at doses > 100 mg m-2 has been reported in the literature predominantly using autologous bone marrow rescue (ABMR).…”

Section: Patientsmentioning

confidence: 99%

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Granulocyte-macrophage colony stimulating factor (GM-CSF) after high-dose melphalan in patients with advanced colon cancer

Steward

Scarffe²,

Dirix³

et al. 1990

Br J Cancer

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Nine patients with progressive, metastatic disease from primary carcinoma of the colon were entered into a phase I/II study using continuous intravenous infusions of granulocyte-macrophage colony-stimulating factor (GM-CSF) and high dose melphalan (120 mg m-2). GM-CSF was given alone to six patients during the first part of the study to determine a dose that would produce a peripheral leucocyte count (WCC) greater than or equal to 50 X 10(9) 1(-1) and was initially given at 3 micrograms kg-1 day-1 and escalated to 10 micrograms kg-1 day-1 after 10 days. The infusion was discontinued when the WCC exceeded 50 X 10(9) 1(-1) and after a gap of one week, melphalan was given over 30 min. GM-CSF was recommenced 8 h later and was continued until the neutrophil count had exceeded 0.5 X 10(9) 1(-1) for greater than 1 week. One patient achieved a WCC greater than 50 X 10(9) 1(-1) with GM-CSF 3 micrograms kg-1 day-1, but the other five who entered this phase of the study required dose escalation to 10 micrograms kg-1. No toxicity attributed to GM-CSF was seen. After melphalan, the median times to severe neutropenia (less than 0.5 X 10(9) 1(-1] and thrombocytopenia (greater than 20 X 10(9) 1(-1] were 6 and 9 days respectively. The median durations of neutropenia and thrombocytopenia were 14 and 10 days respectively. All patients required intensive support with a median duration of inpatient stay of 24 days. There was one treatment related death due to renal failure. One complete and two partial remissions (33% response rate) were seen but these were of short duration (median of 10 weeks). This study demonstrates that GM-CSF given by continuous intravenous infusion produces significant increments of peripheral granulocyte counts at 3 and 10 micrograms kg-1 day-1 and is not associated with any toxicity. The duration of neutropenia and thrombocytopenia induced by high-dose melphalan appears to be reduced by the subsequent administration of GM-CSF to times which are at least as short as have been reported in historical series which have used autologous bone marrow rescue.

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Section: Patientssupporting

confidence: 53%

Section: Patientsmentioning

confidence: 99%

Granulocyte-macrophage colony stimulating factor (GM-CSF) after high-dose melphalan in patients with advanced colon cancer

Steward

Scarffe²,

Dirix³

et al. 1990

Br J Cancer

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“…12,17 Where thiotepa and Mel are strongly myeloablative even as single agents, this is not the case for etoposide. [18][19][20] In the late 70's, etoposide was shown to be able to induce remission in 15-25% of patients with AML who had failed to remit after standard regimens used at that time. 21 These experiences led to the incorporation of this drug into the standard induction courses for newly diagnosed AML.…”

Section: Discussionmentioning

confidence: 99%

Allo-SCT using BU, CY and melphalan for children with AML in second CR

Beier

Albert

Bader

et al. 2012

Bone Marrow Transplant

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Based on the results from the AML-BFM 98 trial, hematopoietic SCT (HSCT) is recommended for children with AML in second CR only. Here, we retrospectively analyze interphase data of children who underwent HSCT after myeloablative conditioning with BU, CY, and melphalan (BuCyMel) for AML in second remission (CR2) between 1998 and 2009. Out of 152 children, transplant data were available on 109 individuals. Sixty out of 109 children (55%) received BuCyMel. Median age at HSCT was 12.2 years (range 3.0; 18.3). GVHD prophylaxis mostly consisted of CsA and short term MTX with or without antithymocyte globulin. Matched-sibling donors were used for 6/60 analyzed recipients, the remainder either received grafts from matched unrelated (30/60) or mismatched donors. OS after 5 years was 62% (s.e. 6%), relapse incidence 35% (18/60 children) and treatment-related mortality accounted for 12% (7/60) of fatal events. In conclusion, even taking into account possible selection bias in this retrospective analysis, HSCT in CR2 using BuCyMel resulted in a respectable OS. Based on this data the prospective, controlled and centrally monitored AML SCT-BFM 2007 trial has started to recruit patients in January 2010 aiming to generate valid outcome data for further strategy decisions.

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“…46 Response rates of 75% have been achieved in high-dose single alkylating agent therapy in failed or refractory breast cancer. [22][23][24] The major obstacle to curing patients with advanced breast cancer and other malignancies with HDC and autologous PBSCT is relapse. 1,[9][10][11][12]32 Strategies to reduce relapse rates include increasing the intensity of the preparative regimen and administering the HDC earlier in the course of the disease when disease burden is small and tumor resistance is less likely to have developed.…”

Section: Upnmentioning

confidence: 99%

“…[19][20][21] Melphalan and thiotepa are among the most active single agents in the treatment of breast and ovarian cancer. 15,[22][23][24][25][26] Similarly, carboplatin as a single agent has significant activity against ovarian, testicular and lung cancer. 3 Carboplatin as a part of ICE (ifosfamide, carboplatin and etoposide) and CTCb (cyclophosphamide, thiotepa, carboplatin) HDC regimens has been used for the treatment of various solid tumors with autologous PBSCT.…”

mentioning

confidence: 99%

A phase I dose escalation study of high-dose thiotepa, melphalan and carboplatin (TMCb) followed by autologous peripheral blood stem cell transplantation (PBSCT) in patients with solid tumors and hematologic malignancies

Demirer

İlhan

Mandel

et al. 2000

Bone Marrow Transplant

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Summary:The purpose of this study was to determine the maximum tolerated dose of carboplatin administered with 500 mg/m 2 thiotepa and 100 mg/m 2 melphalan followed by autologous peripheral blood stem cell (PBSC) infusion in patients with refractory malignancies. Twenty-eight patients with refractory malignancies received high-dose thiotepa (500 mg/m 2 , melphalan (100 mg/m 2 ) and escalating doses of carboplatin 900-1500 mg/m 2 ) followed by infusion of cryopreserved autologous PBSCs. The maximum tolerated doses were determined to be 500 mg/m 2 thiotepa, 100 mg/m 2 melphalan and 1350 mg/m 2 carboplatin. Two consecutive patients receiving 1500 mg/m 2 carboplatin experienced grade 3 mucositis and colitis. Ten patients were enrolled at the maximum tolerated dose and none had grade 3-4 regimen-related toxicity and mortality. All patients at this level experienced grade 1-2 mucositis, 90% grade 1-2 gastrointestinal toxicity, 30% grade 1-2 cardiac and renal toxicity, and 10% experienced grade 1 hepatic toxicity. The median time to achieve a granulocyte count of 0.5 × 10 9 /l was 9 days (range 7-12 days) and platelet count of 20 × 10 9 /l was 10 days (range 7-15 days). Of eight patients with stage IV refractory breast cancer, even were evaluable for response, one patient on day 75 will be evaluated soon. Five of seven (71.5%) evaluable patients achieved a complete remission (CR) and two had no response. Of seven patients with non-Hodgkin's lymphoma (n = 4) or Hodgkin's disease (n = 3), five achieved a CR (71.5%). Thiotepa, melphalan and carboplatin can be administered in high doses with tolerable mucositis as the major side-effect. This combination has significant activity in patients with breast cancer, and phase II studies in patients with breast cancer and other chemotherapy-sensitive malignancies are warranted. Bone Marrow Transplantation (2000) 25, 697-703.

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High–dose melphalan with autologous bone marrow transplant treatment of poor prognosis tumors

Cited by 56 publications

References 16 publications

Granulocyte-macrophage colony stimulating factor (GM-CSF) after high-dose melphalan in patients with advanced colon cancer

Granulocyte-macrophage colony stimulating factor (GM-CSF) after high-dose melphalan in patients with advanced colon cancer

Allo-SCT using BU, CY and melphalan for children with AML in second CR

A phase I dose escalation study of high-dose thiotepa, melphalan and carboplatin (TMCb) followed by autologous peripheral blood stem cell transplantation (PBSCT) in patients with solid tumors and hematologic malignancies

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