Chemotherapy Compared with Autologous or Allogeneic Bone Marrow Transplantation in the Management of Acute Myeloid Leukemia in First Remission

Cassileth, Peter A.; Harrington, David P.; Appelbaum, Frederick R.; Lazarus, Hillard M.; Rowe, Jacob M.; Paietta, Elisabeth; Willman, Cheryl L.; Hurd, David D.; Bennett, John M.; Blume, Karl G.; Head, David R.; Wiernik, Peter H.

doi:10.1056/nejm199812033392301

Cited by 548 publications

(363 citation statements)

References 31 publications

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“…The role of ASCT in AML remains controversial. Phase II and III trials showed that ASCT provides lower relapse rates than conventional CHT and improves DFS in some but not in all studies [3,[7][8][9]. Our retrospective study analyzed the role of ASCT in patients with AML, with good, intermediate and poor prognostic features.…”

Section: Discussionmentioning

confidence: 99%

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Is there still a role for autologous stem cell transplantation in acute myeloid leukemia?

Demečková²,

Bojtárová³

et al. 2012

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Background: the role of autologous stem cell transplantation (ASCT) in treatment of acute myeloid leukemia (AML) remains unsettled. Aims: retrospective analysis to evaluate the role of ASCT in patients with AML without HLA-matched donor. Methods: between December 19, 1994 and August 1, 2012, a total of 63 patients with AML without HLA-matched donor in the department of Hematology and Transfusion Medicine, University Hospital, Bratislava, received an ASCT. Median age was 41 years (20-61 years). There were 35 (56%) males and 28 (44%) females. At the time of ASCT, 50 (79%) patients were in first complete remission (CR), 11 (18%) patients were in second CR and 2 (3%) patients were in relapse. Results: with a median follow-up of 115 months (34-214 months), the 10 year overall survival (OS) and disease free survival (DFS) of all patients was 55% and 51%, respectively. Transplant-related mortality was 6%. The relapse rate was 38% and 9 years probability of relapse was 44%. Conclusion: ASCT is still an effective post-remission treatment in AML patients without HLA-matched donor; with the possibility of long-term survival or even cure in remarkable proportion of patients with AML, particularly in patients with favorable and intermediate cytogenetic risk.

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Section: Discussionmentioning

confidence: 99%

“…In table 3 we compared our results with three large phase III randomized studies [7][8][9], ALWP-EBMT registry [10] and two recent long-term single institution studies [1,4]. It is now well proven that hemopoiesis recovery (engraftment) is more rapid with PBSCT than with BMSCT [11][12][13].…”

Section: Discussionmentioning

confidence: 99%

Is there still a role for autologous stem cell transplantation in acute myeloid leukemia?

Demečková²,

Bojtárová³

et al. 2012

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“…As reported in other series [28,45], 25% of eligible patients failed to receive stem cell grafts due to several reasons, including refusal to undergo further therapy. While the groups may not be comparable, patients who completed consolidation treatment but failed to undertake stem cell transplantation had an overall poor outcome (Fig.…”

Section: Discussionmentioning

confidence: 61%

Increasing dose intensity of anthracycline antibiotics improves outcome in patients with acute myelogenous leukemia

et al. 2004

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To understand the effect of dose concentration in the overall survival of AML, we conducted a study on the efficacy and toxicity of a drug combination where the dose of daunorubicin was intensified. For this analysis, the outcome of patients entered into two consecutive prospective trials was compared. Inclusion criteria in both arms were identical and consisted of primary AML in adults. Treatment protocol for Cape Town Regimen 4 (CTR-IV) comprised of cytarabine infusion (100 mg/m 2 ) and etoposide (100 mg/m 2 ), injection daily for 7 days in combination with daunorubicin (45 mg/m 2 ) on days 1, 2, and 3. Patients achieving remission were given two further courses of the same chemotherapy and received allogeneic or autologous transplantation. CTR-V was a similar treatment program, except that daunorubicin was escalated on days 1, 2, and 3 to 75 mg/m 2 during induction and to 60 mg/m 2 during a single consolidation. Patients were also offered stem cell transplantation. Between 1990 and 1997, 78 patients (median age 33; range 13-67 years) fulfilled entry criteria and received CTR-IV. From 1998 onwards, 35 patients (median age 36; range 15-66 years) were prospectively enlisted into the CTR-V trial. The patient population in CTR-V had fewer Caucasian individuals (P = 0.02) and had significantly lower presentation hemoglobin (P = 0.0002). Following initiation of induction chemotherapy, 40 patients failed to respond. Among these, 10 patients demised before day 28. Another 30 (25/69 CTR-IV and 5/32 in CTR-V groups; P = 0.01) had leukemia that was resistant to chemotherapy, and all died. Remission was achieved in 59% of patients treated with CTR-IV and 77% of those receiving CTR-V (P = 0.03). CR occurred with a single course in 64% versus 88% (P = 0.02), respectively. There were no differences in the toxicity profile between these two combinations. Disease recurred in 50% and 28% (P = 0.07) of patients. For the 113 individuals, median follow up is 254 (range 19-4,451) and 304 (12-1,702; P = 0.03) days. Survival is 23% and 40%, respectively, favoring patients treated with CTR-V (log rank; P = 0.03). Cox regression analysis showed that treatment group (P < 0.001), FAB type, hemoglobin level, and platelet count were independent factors for response to chemotherapy. Older age and not undergoing myeloablative therapy were the only adverse factors for survival. We conclude that increase in the treatment dose of daunorubicin in patients with AML led to a higher remission rate, particularly with a single course of chemotherapy and had an equivalent toxicity profile. This therapeutic modification is also likely to result in substantial reduction in patient stay in hospital and in the overall expenditure. Am.

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“…Whether such patients should receive high-dose ara-C based chemotherapy alone or undergo autologous or allogeneic stem cell transplantation remains unsettled. Several large prospective studies have failed to demonstrate a consistently superior survival for one therapy over another [38,39]. Most, [40,41]but not all, [42] trials have failed to document a benefit for the addition of low dose (maintenance) chemotherapy after intensive post-remission therapy.…”

Section: Discussionmentioning

confidence: 99%

Low dose interleukin‐2 following intensification therapy with high dose cytarabine for acute myelogenous leukemia in first complete remission

et al. 2008

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The most important problem in the therapy of patients with acute myeloid leukemia (AML) is relapse after intensive therapy. We sought to determine if interleukin-2 (low-dose with intermittent boluses) administration could be feasibly administered after standard therapy to potentiate anti-tumor immunity in a fashion analogous to the post-allogeneic stem cell transplant ''graft-vs-leukemic'' effect. Adults with de novo AML received daunorubicin and cytosine arabinoside induction therapy. Patients achieving complete remission received high dose ara-C (HIDAC) for three courses followed by low dose rIL-2 (Amgen), administered by continuous infusion (450,000 U/m 2 /day) for 10 weeks with intermittent boluses (500,000/U/m 2 over 2 hr) given in weekly intervals starting on Week 4. Of the 32 enrolled patients, 27 achieved CR; 8/11 who received rIL-2 completed therapy. 6/11 are long term survivors (median follow-up, 139 months). rIL-2 was well tolerated and associated with a 5-fold increase in circulating NK-lymphocytes and a 3-fold increase in circulating T-cells. Mononuclear cells from patients receiving rIL-2 exhibited enhanced cytolytic activity in vitro against cryopreserved autologous leukemia cells. This study supports further investigation of immunotherapy in the post-intensive chemotherapy setting in the management of patients with AML. Am. J. Hematol. 83:771-777, 2008. V

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Chemotherapy Compared with Autologous or Allogeneic Bone Marrow Transplantation in the Management of Acute Myeloid Leukemia in First Remission

Abstract: A postinduction course of high-dose cytarabine can provide equivalent disease-free survival and somewhat better overall survival than autologous marrow transplantation in adults with acute myeloid leukemia.

Cited by 548 publications

References 31 publications

Is there still a role for autologous stem cell transplantation in acute myeloid leukemia?

Is there still a role for autologous stem cell transplantation in acute myeloid leukemia?

Increasing dose intensity of anthracycline antibiotics improves outcome in patients with acute myelogenous leukemia

Low dose interleukin‐2 following intensification therapy with high dose cytarabine for acute myelogenous leukemia in first complete remission

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Chemotherapy Compared with Autologous or Allogeneic Bone Marrow Transplantation in the Management of Acute Myeloid Leukemia in First Remission

Abstract: A postinduction course of high-dose cytarabine can provide equivalent disease-free survival and somewhat better overall survival than autologous marrow transplantation in adults with acute myeloid leukemia.

Cited by 548 publications

References 31 publications

Is there still a role for autologous stem cell transplantation in acute myeloid leukemia?

Is there still a role for autologous stem cell transplantation in acute myeloid leukemia?

Increasing dose intensity of anthracycline antibiotics improves outcome in patients with acute myelogenous leukemia

Low dose interleukin‐2 following intensification therapy with high dose cytarabine for acute myelogenous leukemia in first complete remission

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Product

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Is there still a role for autologous stem cell transplantation in acute myeloid leukemia?

Is there still a role for autologous stem cell transplantation in acute myeloid leukemia?