In vivo purging with high-dose cytarabine followed by high-dose chemoradiotherapy and reinfusion of unpurged bone marrow for adult acute myelogenous leukemia in first complete remission.

Stein, Anthony S.; O’Donnell, Margaret; Chai, Aaron; Schmidt, GM; Nademanee, AP; Parker, Pablo; Smith, Eileen; Snyder, David S.; Molina, Arturo; Stepan, DE; Spielberger, Ricardo; Somlo, George; Margolin, Kim; Vora, Nayana; Lipsett, James A.; Lee, J; Niland, Joyce C.; Forman, Stephen J.

doi:10.1200/jco.1996.14.8.2206

Cited by 52 publications

(23 citation statements)

References 40 publications

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“…Prior HDAC may have contributed to delayed engraftment. Stein et al 20 reported engraftment data which are similar to ours using unpurged bone marrow collected after post-remission therapy including HDAC. Alternatively, the use of HDAC remission induction therapy may have had a beneficial effect.…”

Section: Discussionsupporting

confidence: 72%

Autologous bone marrow transplantation for acute myeloid leukemia using 4-hydroperoxycyclophosphamide-purged bone marrow and the busulfan/etoposide preparative regimen: a follow-up report

Linker

Ries

Damon

et al. 1998

Bone Marrow Transplant

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Summary:We studied the use of autologous bone marrow transplantation (ABMT) as treatment for acute myeloid leukemia (AML) in adults up to age 60. We used a preparative regimen of busulfan 16 mg/kg plus etoposide 60 mg/kg and bone marrow purged with 100 g/ml of 4-hydroperoxycyclophosphamide (4HC). We treated 50 first remission patients; there were two treatmentrelated deaths and 13 relapses. With median follow-up of 6.8 years (minimum 4.5) disease-free survival (DFS) is 70%, relapse rate 27% and overall survival 72%. Patients with favorable cytogenetics had DFS 78% and relapse 18% whereas unfavorable patients had DFS 63% and relapse rate 35%. For 25 patients in second or third remission there were five treatment-related deaths and seven relapses. DFS is 52% and relapse rate 35%. None of six patients with primary refractory AML had long-term disease control. These data support the use of ABMT with an intensive preparative regimen and purged bone marrow as a highly effective treatment for adults with AML. Keywords: ABMT; AML; 4HC During the past decade there have been a number of improvements in the treatment of young adults with acute myeloid leukemia. All-trans retinoic acid (ATRA) has been identified as an important new agent in the treatment of acute promyelocytic leukemia. 1 High-dose Ara-C (HDAC) has been confirmed as superior to standard-dose Ara-C for post-remission therapy. 2 HDAC has been identified as especially helpful in the favorable cytogenetic groups with t(8; 21) and inversion 16q. 3 However, the majority of young adults with AML lacking favorable prognostic factors still fare poorly with conventional chemotherapy. Even with the use of repeated courses of HDAC post-remission therapy, only 20-25% of these patients will remain in long-term remission. 2 Experience with allogeneic bone marrow transplantation demonstrates that intensive therapies can lower the relapse rate and improve disease-free survival (DFS) for young adults with AML. 4 Furthermore, studies comparing preparative regimens have demonstrated the principle that more intensive preparative regimens can lower the relapse rate. 5 However, in the allogeneic transplant setting, these improvements in disease control have been offset by increases in treatment-related mortality (TRM). The use of targeted radiation through radioimmunoconjugates has produced very promising results and may allow this impasse to be broken. 6 Although allogeneic transplantation consistently produces improved DFS when compared to conventional chemotherapy, this treatment is limited by donor availability and by the 25% TRM which raises the question as to whether reserving allogeneic transplant as a salvage therapy would be an equal or better strategy.Autologous bone marrow transplantation (ABMT) has been actively investigated as an alternative way to improve outcome for AML patients. The treatment is attractive because of the potential for broad use in adults up to and perhaps beyond age 60 and because of relatively low TRM. Because of the absence of graft-versus-host ...

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Section: Discussionsupporting

confidence: 72%

Autologous bone marrow transplantation for acute myeloid leukemia using 4-hydroperoxycyclophosphamide-purged bone marrow and the busulfan/etoposide preparative regimen: a follow-up report

Linker

Ries

Damon

et al. 1998

Bone Marrow Transplant

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“…13 Mobilization of PBPCs by the use of high-dose chemotherapy alone or in combination with growth factors, such as GM-CSF or G-CSF, may produce a sufficient number of progenitor cells to ensure early engraftment and serve as a means of reducing potential leukemia cell contamination. 14,15 In order to assess the long-term outcome of myeloablative preparative conditioning without the high TRM and mortality of either allogeneic transplantation or purged autologous PBPCs, we evaluated the risk of relapse, LFS, and overall survival in 129 patients with AML in CR1 treated with high-dose chemoradiotherapy followed by the infusion of autologous PBPCs procured after high-dose consolidation chemotherapy as a form of in vivo purging. This large group of patients, followed over a 10-year period, represents a population of adult leukemia patients unrestricted on the basis of age or prognostic features.…”

Section: Introductionmentioning

confidence: 99%

Long-term outcome of autologous transplantation of peripheral blood progenitor cells as postremission management of adult acute myelogenous leukemia in first complete remission

et al. 2003

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In order to improve leukemia-free survival (LFS) without the treatment-related morbidity of allogeneic bone marrow transplantation or multiple prolonged cycles of consolidation chemotherapy, we evaluated the long-term outcome of autologous transplantation of peripheral blood progenitor cells (PBPCs) as postremission therapy in 129 patients aged 18-71 years (median 49 years) with newly diagnosed acute myelogenous leukemia (AML) in first complete remission (CR1). The median follow-up from remission for surviving patients was 62.2 months (range 3.7-127.9 months). A total of 57 patients were alive and leukemia free at the end of the study. The LFS and overall survival 5 years from remission were 40.2% (79.2%) and 41.4% (79.4%), respectively. The median LFS and overall survival are 17.3 and 23.3 months, respectively. Multivariate analysis identified age as the most significant predictor for both LFS and overall survival. Karyotype was also found to be predictive of outcome. Our results show that autologous transplantation of PBPC procured after a single cycle of highdose cytarabine-based consolidation chemotherapy for a population of adult patients with AML in CR1 produces a high likelihood of long-term LFS, offering a state of clinical minimal residual disease for the investigation of future therapeutic approaches.

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“…Indeed, the rate of severe toxicity (most particularly infectious complications) after EMA chemotherapy was relatively high. Toxicity of WHO grade more than 2 following EMA therapy was observed in 23% of cases and did not compare favorably to the 8% previously reported by Stein et al 22 with high-dose cytarabine in AML from all subtypes. Failure of harvesting could be exceptionally related to prior treatment by ATRA and early intensification chemotherapy.…”

Section: Discussionmentioning

confidence: 65%

Treatment of relapsing acute promyelocytic leukemia by all-trans retinoic acid therapy followed by timed sequential chemotherapy and stem cell transplantation

Thomas

Dombret

Cordonnier³

et al. 2000

Leukemia

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The purpose of this study was to assess the safety and efficacy of stem cell transplantation (SCT) mainly autologous SCT as consolidation therapy in APL patients who relapsed and achieved a second complete remission (CR2). Fifty adult patients with a first relapsed APL, of whom 39 had been previously treated with ATRA, entered a multicenter trial of oral ATRA until complete remission (CR) achievement followed by timed sequential chemotherapy (EMA combining etoposide 200 mg/m 2 /day for 3 days, mitoxantrone 12 mg/m 2 /day for 3 days, and cytarabine 500 mg/m 2 /day for two sequences of 3 days). EMA was started either after CR achievement, or on day 1 of ATRA because of initial white blood cell (WBC) counts Ͼ5 × 10 9 /l, or rapidly added to ATRA in order to prevent ATRA syndrome because WBC count increased under ATRA. Forty-five patients (90%, 95% CI 78%-97%) were in CR after induction therapy. Five patients died from infection during aplasia following EMA chemotherapy. Eleven patients who achieved CR had a familial HLA-identical donor and were allografted. The median disease-free survival (DFS) of allografted patients was 8.2 months. The 34 other CR patients were scheduled for autologous peripheral blood (PB) SCT (intent-to-treat group). Actually, autologous transplantation was only carried out in 22 patients (65%) (17 PBSCT and five autologous bone marrow transplantation (BMT)). Reasons for not autografting were early relapse (three patients), severe toxicity of EMA chemotherapy (six patients), and refusal or failure of stem cell harvest (three patients). The 3-year DFS rate of patients actually autografted was 77%. Among the 17 autografted patients still in CR2, nine patients have already reached a longer CR2 than first CR (CR1). Results of detection of PML/RAR␣ by RT-PCR after autologous transplantation show negative findings in eight of the nine patients tested. We conclude that (1) ATRA combined to EMA chemotherapy is effective in the treatment of relapsed APL; (2) allogeneic BMT may be too toxic after salvage treatment including EMA intensive chemotherapy; (3) clinical outcome of autografted patients and preliminary molecular results regarding detection of PML/RAR␣ after autologous PBSCT are encouraging. Leukemia (2000) 14, 1006-1013.

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In vivo purging with high-dose cytarabine followed by high-dose chemoradiotherapy and reinfusion of unpurged bone marrow for adult acute myelogenous leukemia in first complete remission.

Abstract: This approach offers a relatively high DFS rate to adult patients with AML in first CR. The results of this study are similar to those achieved with allogeneic BMT.

Cited by 52 publications

References 40 publications

Autologous bone marrow transplantation for acute myeloid leukemia using 4-hydroperoxycyclophosphamide-purged bone marrow and the busulfan/etoposide preparative regimen: a follow-up report

Autologous bone marrow transplantation for acute myeloid leukemia using 4-hydroperoxycyclophosphamide-purged bone marrow and the busulfan/etoposide preparative regimen: a follow-up report

Long-term outcome of autologous transplantation of peripheral blood progenitor cells as postremission management of adult acute myelogenous leukemia in first complete remission

Treatment of relapsing acute promyelocytic leukemia by all-trans retinoic acid therapy followed by timed sequential chemotherapy and stem cell transplantation

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