Favorable Outcomes in Elderly and High-Risk Patients with AML and MDS Following T-Cell Depleted Reduced Intensity Conditioned Allogeneic Stem Cell Transplantation

Abstract Allogeneic hematopoietic stem cell transplantation (HSCT) remains the only curative treatment option for most high-risk patients with acute myeloid leukemia (AML). However, many high-risk patients regenerate with blasts or relapse early after induction therapy. Thus, consolidation with allogeneic HSCT in first CR is often not possible. Performing allogeneic HSCT within induction therapy can circumvent these problems and may furthermore reduce cumulative toxicity in high risk patients. Therefore, the prospective randomized treatment trial AML2003 for patients <= 60 years was set up, to investigate the feasibility and value of an intensified treatment strategy, i.e. early allogeneic stem cell transplantation in aplasia after induction therapy, for high risk AML patients in a multi-center setting. To achieve this goal, rapid analysis of cytogenetics, FLT3 status and HLA-types of the patient and possible family donors is of utmost importance. This fast search diagnostics together with routine analyses of morphology and immunophenotyping is accomplished centrally in all enclosed patients. Furthermore, in all patients the likelihood to find an unrelated donor is checked by an internet search in the BMDW database. Within the first 8 months 107 AML patients with a median age of 48 (17–60) years were included in the study. Fast search diagnostics was complete within a median of 15 (range 5–31) days after arrival of the bone marrow samples for all patients. 57/107 patients were randomized into the intensified treatment arms. Out of these 25 (44%) patients with high risk characteristics have been identified. A suitable related or unrelated donor was found for 22 (88%) of those high-risk patients. Nine of those high risk patients with a donor (41%) received early allogeneic stem cell transplantation in aplasia after the first (n=4) or the second (n=5) induction therapy course on an intend to treat basis within the protocol. Three were transplanted with stem cells of related and six of unrelated donors. The preparative regimen consisted of melphalan 150mg/m2 and fludarabine 150mg/m2. So far no treatment associated death had to be recognized. These encouraging preliminary results show that fast risk-profiling and early donor-search is feasible in a large multi-center study. This leads to a significant proportion of early allogeneic stem cell transplants in aplasia after induction therapy within the group of high risk AML patients, which may improve the disastrous prognosis of this group of patients in the future.

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Upfront Allogeneic Stem Cell Transplantation for Remission Induction in High-Risk Acute Myeloid Leukemia Patients within the Randomized Multi- Center Trial AML2003.

Blood ◽

10.1182/blood.v112.11.978.978 ◽

2008 ◽

Vol 112 (11) ◽

pp. 978-978 ◽

Cited By ~ 3

Author(s):

Markus Schaich ◽

Thomas Illmer ◽

Walter E. Aulitzky ◽

Martin Bornhaeuser ◽

Martin Griesshammer ◽

...

Keyword(s):

Stem Cell ◽

High Risk ◽

Stem Cell Transplantation ◽

Cell Transplantation ◽

Induction Therapy ◽

Allogeneic Stem Cell Transplantation ◽

Allogeneic Transplantation ◽

Remission Induction ◽

High Risk Patients ◽

Risk Patients

Abstract Introduction: Allogeneic hematopoietic stem cell transplantation (HSCT) remains the only curative treatment option for most high-risk patients with acute myeloid leukemia (AML). However, many high-risk patients regenerate with blasts or relapse early after induction therapy. Thus, consolidation with allogeneic HSCT in first CR is often not possible. Performing upfront allogeneic HSCT for remission induction as part of induction therapy has the potential to circumvent these problems and might furthermore reduce cumulative toxicity in high-risk patients. Therefore, in 2003 we started a prospective multicenter randomized trial that investigates both the feasibility and efficacy of upfront allogeneic stem cell transplantation for remission induction in high-risk AML patients. Methods: The AML2003 study compares in a randomized fashion an intensified treatment approach using upfront allogeneic transplantation in high risk patients as part of the induction therapy (IT) during marrow aplasia achieved by DA (daunorubicin 60 mg/ m2 – day 3–5; cytarabine 100 mg/m2 – day1–7) to a “conventional” treatment strategy, which allows for allogeneic transplantation only in patients achieving remission after two induction courses (DA). To do this, rapid analysis of cytogenetics, FLT3 status and HLA-DNA-typing of the patient and possible family donors is of utmost importance. This “fast search diagnostics” together with routine analyses of morphology and immunophenotyping is accomplished centrally in all enclosed patients. The dose-reduced preparative regimen for upfront allogeneic stem cell transplantation within induction therapy consisted of melphalan 150mg/m2 and fludarabine 150mg/m2. Results: Until the last update we recruited 679 patients <= 60 years with de novo (n=570) or secondary (n=109) AML. Out of 340 patients randomized for an intensified treatment approach we identified 139 patients (41%) with high-risk defined by cytogenetic criteria (n=87), FLT3 status (n=15) or day 15 blast count (n=37). Fast search strategy revealed HLA identical donors (related or unrelated) for 106 patients. Consequently, 78 high-risk AML patients assigned to the intensified treatment strategy received allogeneic transplantation. Upfront allogeneic stem cell transplantation for remission induction was feasible in 28 high-risk AML patients during marrow aplasia after IT1 (n=10) or IT2 (n=18), respectively. Fifteen of these patients received unrelated grafts. Conclusions: These preliminary results show that rapid risk profiling and fast donor-search is feasible in a large multi-center study. This leads to a significant proportion of upfront allogeneic stem cell transplants as part of the induction therapy within the group of high-risk AML patients, which may improve the disastrous prognosis of this group of patients in the future.

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