High-dose melphalan for multiple myeloma: long-term follow-up data.

1994 ◽  
Vol 12 (4) ◽  
pp. 764-768 ◽  
Author(s):  
D Cunningham ◽  
L Paz-Ares ◽  
M E Gore ◽  
J Malpas ◽  
T Hickish ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Response Rate ◽  
Autologous Bone Marrow Transplantation ◽  
Autologous Bone Marrow ◽  
High Dose ◽  
Long Term Follow Up ◽  
Autologous Bone ◽  
High Dose Melphalan

PURPOSE To present long-term follow-up data of patients with myeloma treated with high-dose melphalan HDM, including an assessment of prognostic factors. PATIENTS AND METHODS Between November 1981 and April 1986, 63 previously untreated patients with multiple myeloma received HDM 140 mg/m2 without autologous bone marrow transplantation. RESULTS The overall response rate was 82% (51 of 62), with 32% (20 of 62) patients entering complete remission (CR). The median duration of response was 18 months, and six patients remain alive and free from disease progression at 60+ to 84+ months. Improvements in quality of life associated with remission were immediate in terms of pain grade (89% of patients) and performance status (92%), and later in terms of bone healing (29%). Currently, at a median follow-up duration of 74 months (range, 63 to 100) since HDM, 23 patients are alive with a median survival duration of 47 months, and 35% of patients are expected to be alive at 9 years. Apart from early-stage disease, no factors were found to predict long-term survival. No second malignancies or other late side effects have been recorded. CONCLUSION Single-agent HDM without autologous bone marrow transplantation is a feasible therapeutic option in myeloma, and is associated with a high objective response rate, relatively long remission durations, and good symptom control.

scholarly journals High-dose chemoradiotherapy and autologous bone marrow transplantation for resistant multiple myeloma

Blood ◽  
1987 ◽  
Vol 70 (3) ◽  
pp. 869-872 ◽  
Author(s):  
B Barlogie ◽  
R Alexanian ◽  
KA Dicke ◽  
G Zagars ◽  
G Spitzer ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Bone Marrow ◽  
Bone Marrow Transplantation ◽  
Marrow Transplantation ◽  
Autologous Bone Marrow Transplantation ◽  
Autologous Bone Marrow ◽  
High Dose ◽  
Autologous Bone ◽  
Total Body ◽  
High Dose Melphalan

Abstract Seven patients with advanced multiple myeloma, refractory to therapy with alkylating agent-VAD (vincristine-adriamycin-dexamethasone), received a regimen combining high-dose melphalan with total body irradiation supported by autologous bone marrow transplantation. Very rapid, usually greater than 90% tumor mass reduction was achieved in six patients, regardless of prior chemotherapy responsiveness and marrow plasmacytosis up to 30%. Despite signs of early relapse in three patients (median remission duration of all patients, 15 months), five remain alive and well without further cytotoxic therapy from 2 to 21 months (median, 9+ months). Two patients died, one from surgical complications after transplantation and a second due to persistent neutropenia with fatal pneumonia. This treatment provides meaningful disease control for selected patients with resistant myeloma and a poor prognosis.

scholarly journals High-dose melphalan with autologous bone marrow transplantation for multiple myeloma

Blood ◽  
1986 ◽  
Vol 67 (5) ◽  
pp. 1298-1301 ◽  
Author(s):  
B Barlogie ◽  
R Hall ◽  
A Zander ◽  
K Dicke ◽  
R Alexanian
Keyword(s):  
Multiple Myeloma ◽  
Bone Marrow ◽  
Autologous Bone Marrow Transplantation ◽  
Autologous Bone Marrow ◽  
High Dose ◽  
Serious Infections ◽  
High Proliferative Activity ◽  
Autologous Bone ◽  
Marrow Infusion ◽  
High Dose Melphalan

A large dose of melphalan was given to 23 patients with advanced multiple myeloma that was refractory to multiple prior treatments. Sixteen patients received a dose of 80 to 100 mg/m2, and seven were given 140 mg/m2 followed by autologous bone marrow infusion. Tumor mass was reduced by more than 75% in 14 patients, including four who died of bone marrow aplasia. Serious infections were prevented in six of seven patients who received autologous bone marrow. The marked cytoreduction in patients with previously refractory disease indicated the apparent drug resistance could be overcome by dose escalation. However, short remission times in most responding patients were consistent with rapid regrowth of primordial tumor cells with high proliferative activity. Although high-dose melphalan was of limited benefit to patients with refractory myeloma, further studies are necessary to clarify its role during earlier phases of disease.

scholarly journals Long-term follow-up of a phase III study of recombinant human granulocyte-macrophage colony-stimulating factor after autologous bone marrow transplantation for lymphoid malignancies

Blood ◽  
1993 ◽  
Vol 81 (7) ◽  
pp. 1903-1908
Author(s):  
SN Rabinowe ◽  
D Neuberg ◽  
PJ Bierman ◽  
JM Vose ◽  
J Nemunaitis ◽  
...  
Keyword(s):  
Autologous Bone Marrow Transplantation ◽  
Autologous Bone Marrow ◽  
Phase Iii ◽  
Long Term Follow Up ◽  
Macrophage Colony Stimulating Factor ◽  
Autologous Bone ◽  
Macrophage Colony ◽  
Stimulating Factor

One hundred and twenty-eight patients with non-Hodgkin's lymphoma (NHL), Hodgkin's disease (HD), and acute lymphoblastic leukemia (ALL) previously reported from a phase III trial of rhGM-CSF or placebo following autologous bone marrow transplantation (ABMT) were investigated for the development of late toxicities. Median follow-up is 36 months. No apparent long-term deleterious effects on BM function were observed. Moreover, disease-free survival and overall survival were similar for patients on both treatment arms, arguing for the long- term safety of recombinant human granulocyte macrophage-colony- stimulating factor (rhGM-CSF). The only factors predictive for both a high risk of relapse over time and mortality were having the diagnosis of ALL and/or undergoing ABMT in resistant relapse. We attempted to identify clinical variables before BM harvest, at the time of marrow infusion, or events within the first 100 days posttransplant, which might predict speed of neutrophil recovery in the setting of placebo or rhGM-CSF administration after ABMT. Only previous exposure to agents that deplete stem cells led to a significant delay in neutrophil recovery, suggesting their avoidance in patients who may undergo ABMT. Nevertheless, even those patients benefited from rhGM-CSF. For all patients, rhGM-CSF and agents that deplete stem cells were the strongest independent predictors for neutrophil engraftment. With the increasing use of newer hematopoietic growth factors both alone and in combination, long-term follow-up is essential to confirm the same safety that we report with rhGM-CSF.

Autologous Bone Marrow Transplantation for Follicular Lymphoma in First Remission: Long Term Follow up of Two Sequential Trials with Standard Dose and High Dose CHOP Induction.

Blood ◽  
2004 ◽  
Vol 104 (11) ◽  
pp. 5243-5243
Author(s):  
Arnold S. Freedman ◽  
John G. Gribben ◽  
Donna Neuberg ◽  
Sigui Li ◽  
Helen Kim ◽  
...  
Keyword(s):  
Overall Survival ◽  
Standard Dose ◽  
Autologous Bone Marrow Transplantation ◽  
Autologous Bone Marrow ◽  
High Dose ◽  
High Dose Therapy ◽  
First Remission ◽  
Autologous Bone

Abstract High dose therapy and autologous stem cell transplantation (ASCT) has been employed as salvage therapy for patients (pts) with relapsed follicular non-Hodgkin’s lymphoma (FL). Recently, the randomized European CUP trial demonstrated that following 3 cycles of CHOP, ASCT significantly improved both disease free and overall survival when compared to continued CHOP in pts with relapsed FL. In an attempt to improve the results of high dose therapy in FL, we undertook 2 sequential studies for pts with FL in first remission. In the first study, 77 pts with previously untreated advanced stage FL (median age 43), received 6–8 cycles of standard dose CHOP (SD-CHOP) + involved field radiotherapy followed by high dose chemoradiotherapy and anti-B cell purged autologous bone marrow transplantation (ABMT). Following SD-CHOP induction, 27 of 77 pts (36%) were in CR and 50 in a minimal disease state (< 2 cm masses, < 20% BM involvement). At BM harvest, 36 pts had histologic evidence of BM involvement. In the second trial, 19 pts with advanced stage disease (median age 44) were treated with 4 cycles of dose intensified CHOP (HD-CHOP) (cyclophosphamide 1.5 g/m2 day 1 and 2) with G-CSF support followed by high dose chemoradiotherapy and anti-B cell purged autologous ABMT. Following HD-CHOP, 13 of 19 pts were in CR. At BM harvest, 7 of the 19 HD-CHOP pts had histologic BM involvement. Following ABMT, there were 2 acute in-hospital deaths in the pts receiving SD-CHOP induction and none in the pts who received HD-CHOP induction. Nine late deaths in remission were observed in the SD-CHOP pts including 6 from MDS/AML, and 2 late deaths in the HD-CHOP pts. Thirty-three pts who received SD-CHOP remain alive without relapse, with a median follow up of 12 years. Ten pts who received HD-CHOP induction remain alive without relapse, with a median follow up of 9.1 years. For pts receiving SD-CHOP induction, the DFS and overall survival at 10 years are 42% (90% CI: 33%–52%) and 64% (90% CI: 55%–73%), respectively. For pts who received HD-CHOP induction, the DFS and overall survival at 10 years are 59% (90% CI: 38%–79%) and 75% (90% CI: 57%–93%), respectively. The impact of BM treatment and DFS was examined. Pts with known bcl-2 translocations for whom post-BM purging samples were available for pcr examination were analyzed. Following ABMT, pts who were reinfused with pcr negative BM had a significantly better DFS than the pts who were reinfused with pcr positive BM. This study suggests that a subset of pts with FL experience long term remission following ABMT in first remission.

scholarly journals High-dose chemoradiotherapy and autologous bone marrow transplantation for resistant multiple myeloma

Blood ◽  
1987 ◽  
Vol 70 (3) ◽  
pp. 869-872 ◽  
Author(s):  
B Barlogie ◽  
R Alexanian ◽  
KA Dicke ◽  
G Zagars ◽  
G Spitzer ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Bone Marrow ◽  
Bone Marrow Transplantation ◽  
Marrow Transplantation ◽  
Autologous Bone Marrow Transplantation ◽  
Autologous Bone Marrow ◽  
High Dose ◽  
Autologous Bone ◽  
Total Body ◽  
High Dose Melphalan

Seven patients with advanced multiple myeloma, refractory to therapy with alkylating agent-VAD (vincristine-adriamycin-dexamethasone), received a regimen combining high-dose melphalan with total body irradiation supported by autologous bone marrow transplantation. Very rapid, usually greater than 90% tumor mass reduction was achieved in six patients, regardless of prior chemotherapy responsiveness and marrow plasmacytosis up to 30%. Despite signs of early relapse in three patients (median remission duration of all patients, 15 months), five remain alive and well without further cytotoxic therapy from 2 to 21 months (median, 9+ months). Two patients died, one from surgical complications after transplantation and a second due to persistent neutropenia with fatal pneumonia. This treatment provides meaningful disease control for selected patients with resistant myeloma and a poor prognosis.

scholarly journals Long-term follow-up of a phase III study of recombinant human granulocyte-macrophage colony-stimulating factor after autologous bone marrow transplantation for lymphoid malignancies

Blood ◽  
1993 ◽  
Vol 81 (7) ◽  
pp. 1903-1908 ◽  
Author(s):  
SN Rabinowe ◽  
D Neuberg ◽  
PJ Bierman ◽  
JM Vose ◽  
J Nemunaitis ◽  
...  
Keyword(s):  
Autologous Bone Marrow Transplantation ◽  
Autologous Bone Marrow ◽  
Phase Iii ◽  
Long Term Follow Up ◽  
Macrophage Colony Stimulating Factor ◽  
Autologous Bone ◽  
Macrophage Colony ◽  
Stimulating Factor

Abstract One hundred and twenty-eight patients with non-Hodgkin's lymphoma (NHL), Hodgkin's disease (HD), and acute lymphoblastic leukemia (ALL) previously reported from a phase III trial of rhGM-CSF or placebo following autologous bone marrow transplantation (ABMT) were investigated for the development of late toxicities. Median follow-up is 36 months. No apparent long-term deleterious effects on BM function were observed. Moreover, disease-free survival and overall survival were similar for patients on both treatment arms, arguing for the long- term safety of recombinant human granulocyte macrophage-colony- stimulating factor (rhGM-CSF). The only factors predictive for both a high risk of relapse over time and mortality were having the diagnosis of ALL and/or undergoing ABMT in resistant relapse. We attempted to identify clinical variables before BM harvest, at the time of marrow infusion, or events within the first 100 days posttransplant, which might predict speed of neutrophil recovery in the setting of placebo or rhGM-CSF administration after ABMT. Only previous exposure to agents that deplete stem cells led to a significant delay in neutrophil recovery, suggesting their avoidance in patients who may undergo ABMT. Nevertheless, even those patients benefited from rhGM-CSF. For all patients, rhGM-CSF and agents that deplete stem cells were the strongest independent predictors for neutrophil engraftment. With the increasing use of newer hematopoietic growth factors both alone and in combination, long-term follow-up is essential to confirm the same safety that we report with rhGM-CSF.

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