Strong impact of extramedullary involvement in high-risk AML patients with active disease receiving the FLAMSA conditioning regimen for HSCT

Bohl, Stephan R; Harsdorf, Stephanie von; Mulaw, Medhanie A.; Hofmann, Susanne; Babiak, Anna; Maier, Claus‐Philipp; Schnell, Jacqueline; Hütter-Krönke, L-M; Scholl, Katrina; Wais, Verena; Schlenk, Richard F.; Bullinger, Lars; Ringhoffer, Mark; Döhner, Hartmut; Bunjes, Donald; Bommer, Martin; Kuchenbauer, Florian

doi:10.1038/bmt.2016.4

Cited by 6 publications

(7 citation statements)

References 9 publications

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“…A total of eighteen articles underwent full-text review and 9 of them were excluded because they did not report the primary outcomes of interest. Finally, 12 studies fulfilled the eligibility criteria and were included in the meta-analysis [3,6,7,8,9,10,11,12,13,14,15,16]. A manual review of the bibliography of the included studies, and some selected review articles, did not yield any additional eligible studies.…”

Section: Resultsmentioning

confidence: 99%

“…The follow-up period ranged from 0.7 to 145 months. The pooled 1-, 2- and 3-year OS rates were 59.6% (95% CI, 47.9–70.2%; I 2 94%; Figure 2A) [6,7,8,14,15,16], 48.4% (95% CI, 37.3–59.6%; I 2 96%; Figure 2B [3,6,8,10,13,14,15,16], and 40.2% (95% CI, 28.0–53.7%; I 2 96%; Figure 2C) [6,7,11,12,14,15,16], respectively. The pooled 1-, 2- and 3-year LFS were 57.4% (95% CI, 38.6–74.2%; I 2 98%; Figure 2D) [6,14,15,16], 49.4% (95% CI, 38.1–60.8%; I 2 95%; Figure 2E [3,6,9,13,14,15,16], and 39.3% (95% CI, 26.4–53.9%; I 2 97%; Figure 2F) [6,7,12,14,15,16], respectively.…”

Section: Resultsmentioning

confidence: 99%

“…Given, that only 46% of AML patients with induction failure respond to chemotherapy and that 52% with refractory disease die within 90 days [25], FLAMSA-RIC is a reasonable treatment option for this otherwise difficult to treat patient cohort. Interestingly, Bohl et al recently showed a correlation between tumor load and outcome for FLAMSA-RIC, underscoring the relevance of a high tumor burden as one of the strongest negative predictors for treatment outcome after HSCT especially in relapsed or refractory AML patients [8]. Although Goyal et al showed that the exclusive presence of extramedullary disease did not impact on outcome after HSCT [26], Bohl et al noted that that FLAMSA-RIC followed by HSCT is not effective in patients with concurrent active bone marrow and extramedullary disease [8], which led to a change of practice in our institution.…”

Section: Discussionmentioning

confidence: 99%

“…Complete remission (CR) was defined as bone marrow blasts of < 5%, the absence of circulating blasts and blasts with Auer rods, the absence of an extramedullary disease, an absolute neutrophil count (ANC) of ≥ 1.0 × 10 9 /L and a platelet count of ≥ 100 × 10 9 /L [8]. Refractory AML was defined as failure to achieve CR following induction or salvage chemotherapy.…”

Section: Methodsmentioning

confidence: 99%

“…The combination of fludarabine, amsacrine, and cytarabine (FLAMSA)-polychemotherapy with RIC was initially adopted by Schmid et al for patients with high-risk myelodysplastic syndrome (MDS) and acute myeloid leukemia (AML) [3,4,5] to combine high anti-leukemic activity with the advantages of RIC. Although several variations have been published [6,7,8,9,10,11,12,13,14,15,16], the ‘classic’ FLAMSA-RIC regimen consists of fludarabine, amsacrine, and cytarabine, followed by RIC with 4-Gy total body irradiation (TBI), high-dose cyclophosphamide (Cy), antithymocyte globulin (ATG), and prophylactic donor lymphocyte infusions (DLI) if indicated. Because of initially promising data, especially in poor prognosis AML patients, FLAMSA-RIC was adopted by many transplantation centers, and variations that included busulfan (Bu) or treosulfan were established.…”

Section: Introductionmentioning

confidence: 99%

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FLAMSA-RIC for Stem Cell Transplantation in Patients with Acute Myeloid Leukemia and Myelodysplastic Syndromes: A Systematic Review and Meta-Analysis

Owattanapanich

Ungprasert

Wais

et al. 2019

JCM

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Reduced-intensity conditioning (RIC) regimens are established options for hematopoietic stem cell transplantation (HSCT) for patients with acute myeloid leukemia (AML) and myelodysplastic syndrome (MDS). However, the efficacy of RIC regimens for patients with high-risk disease is limited. The addition of a fludarabine, amsacrine, and cytarabine (FLAMSA)-sequential conditioning regimen was introduced for patients with high-risk MDS and AML to combine a high anti-leukemic activity with the advantages of RIC. The current systematic literature review and meta-analysis was conducted with the aim of identifying all cohort studies of patients with AML and/or MDS who received FLAMSA-RIC to determine its efficacy and toxicity. Out of 3044 retrieved articles, 12 published studies with 2395 overall patients (18.1–76.0 years; 96.8% AML and 3.2% MDS; follow-up duration of 0.7–145 months; 50.3% had active AML disease before HSCT) met the eligibility criteria and were included in the meta-analysis. In the pooled analysis, the 1- and 3-year overall survival (OS) rates were 59.6% (95% confidence interval (CI), 47.9–70.2%) and 40.2% (95% CI, 28.0–53.7%), respectively. The pooled 3-year OS rate of the patients who achieved CR1 or CR2 prior to HSCT was 60.1% (95% CI, 55.1–64.8%) and the percentage of those with relapse or refractory disease was 27.8% (95% CI, 23.3–32.8%). The pooled 3-year leukemia-free survival (LFS) rate was 39.3% (95% CI, 26.4–53.9%). Approximately 29% of the patients suffered from grades 2–4 acute graft-versus-host disease (GVHD), while 35.6% had chronic GVHD. The pooled 1- and 3-year non-relapse mortality (NRM) rates were 17.9% (95% CI, 16.1–19.8%) and 21.1% (95% CI, 18.8–23.7%), respectively. Our data indicates that the FLAMSA-RIC regimen is an effective and well-tolerated regimen for HSCT in patients with high-risk AML and MDS.

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